Medical devices to limit movement of breast implants

ABSTRACT

Breast fixation devices for use in breast reconstruction and breast augmentation limit the rotation or movement of breast implants after implantation that results in an unnatural appearance of the breast. The breast fixation devices can include a thin-walled enclosure in the shape of a pouch. A breast implant is secured inside the pouch to limit movement by applying compression to the breast implants, or using a mating or interlocking mechanism between the pouch and breast implant. The pouches containing the breast implants are implanted in the breast. Tissue in-growth into the pouch limits movement of the pouch-breast implant assembly and thereby limits rotation, migration, and displacement of the breast implant. The pouches preferably comprise poly-4-hydroxybutyrate or copolymer thereof.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims priority to U.S. Ser. No. 62/740,146,filed Oct. 2, 2018, and U.S. Ser. No. 62/868,298, filed Jun. 28, 2019,each of which is incorporated in its entirety by reference for allpurposes.

FIELD OF THE INVENTION

The present invention generally relates to the field of surgery, andmore particularly, to implantable medical devices that limit themovement of breast implants following breast reconstruction, includingaugmentation mastopexy.

BACKGROUND OF THE INVENTION

Breast reconstruction following mastectomy has become an integral andimportant part of breast cancer treatment with the surgery providing thepatient with both aesthetic and psychosocial benefits. Nearly 65% of USbreast reconstruction procedures now use a tissue expander (TE) which istemporarily implanted in the breast to create a pocket for a permanentbreast implant in the first step of the procedure. Tissue expanders arenow more frequently placed on top of the chest muscle (pre-pectoralplacement) rather than under the chest muscle in order to reducepost-operative pain. Once a pocket is created, the TE is removed andreplaced with a permanent breast implant in a second step. In somepatients, however, it is possible to form a pocket for the breastimplant following mastectomy without the use of a TE.

Breast implants can also be used in breast augmentation and mastopexyprocedures to augment breast size. In the latter procedure, a breastlift is combined with breast augmentation. Most commonly, the breastimplant is placed in a pocket under the breast tissue, but in somecases, it is implanted under the chest wall.

Breast implants differ in dimensions, shape, and surface texture. A widevariety of different dimensions are available allowing the surgeon andpatient to select from a range of projections, heights, widths andoverall volume. In terms of shape, there are round and anatomicallyshaped implants, and the surfaces of the implants may be smooth,micro-textured or macro-textured. The Siltex 1600 micro-textured breastimplant, for example, has a surface with small open-pores of 70-150 μmdiameters and depths of 40-100 μm, while the Biocell RTV macro-texturedbreast implant has larger open pores of 600-800 μm diameter with depthsof 150-200 μm (Domino et al. Comparison of the capsular response to theBiocell RTV and Mentor 1600 Siltex breast implant surface texturing: ascanning electron microscopic study, Plastic and Reconstructive Surgery,2001, 108(7), 2047-2052).

Recent studies using high-resolution ultrasound, however, havediscovered that macro-texturing is not sufficient to prevent breastimplant rotation. Sieber et al. (Clinical evaluation of shaped gelbreast implant rotation using high-resolution ultrasound, AestheticSurgery Journal, 2017, Vol 37 (3), 290-296) have reported that theimplant rotation rate in patients implanted with anatomical breastimplants manufactured by Mentor and Allergan was 27%. Furthermore, astaggering 26% of the implants checked had rotated ≥45° from themidline. Sieber et al. concluded that rotation of breast implants wasoccurring in 42% of patients.

Rotation of anatomic breast implants is clearly a major problem becausethe capsule that forms around the implant cannot latch onto the implantand hold it in place. No patient wants to find out that their anatomicalimplant has rotated, and that the thicker part of the implant is nolonger located at the bottom of the breast, but instead is located tothe side or even at the top of the breast. Particularly when the onlyway to resolve the problem is by further surgery.

Concern over the use of macro-textured anatomical breast implants is notlimited to undesirable rotation of the implants resulting in asuboptimal appearance of the breasts. A growing body of evidence isassociating the use of these implants with a serious rise in cases ofanaplastic large cell lymphoma (ALCL), a rare peripheral T-celllymphoma, that can be fatal (Leberfinger et al., Breast-implantassociated anaplastic large cell lymphoma: a systematic review, JAMASurg. 2017, Dec. 1; 152(12), 1161-1168), Chronic inflammation resultingfrom the macro-texturing of the anatomical breast implants is thought tobe the underlying mechanism. The chronic inflammation is believed incertain cases to trigger a malignant transformation of T cells resultingin a cancer of the immune system. Treatment of the lymphoma involvesremoval of the patient's implant and the capsule surrounding theimplant, and in more advanced cases, the patient may require furthertreatment including radiotherapy, chemotherapy, and lymph nodedissection. On account of the rise in cases of breast implant-ALCL, theFDA has advised patients to discuss the risks associated with breastimplants that have macro-textured surfaces, as well as smooth surfaces,and some surgeons are decreasing or discontinuing their use ofmacro-textured breast implants.

While rotation of smooth breast implants does not necessarily change theappearance of the breast, breast implant-ALCL with smooth breastimplants has been reported albeit at a lower incidence rate than withpatients implanted with macro-textured anatomical implants. Furthermore,it has been reported that the rate of capsular contraction, whichresults from a thickening of the thin flexible capsule that initiallysurrounds the implant, is higher for smooth implants than for anatomicalimplants (Damino, et at, Comparison of the capsular response to theBiocell RTV and Mentor 1600 Siltex breast implant surface texturing: ascanning electron microscopic study, Plast. Reconstr. Surg. 2001,108(7), 2047-2052). While the reason for the greater rate of capsulecontraction is not fully understood, it has been postulated that thehigher rate of capsule contraction results from a higher rate ofrotation and more movement of the smooth round breast implants. Capsularcontraction can be a serious problem, and is relatively common. It canoccur soon after implantation or 20-30 years later. Contraction of thecapsule that forms around the implant can cause chronic pain, and afeeling of tightness around the breast. This can be treated either bycapsulotomy where the implant is removed, incisions are made in thecapsule, and the implant is replaced. Or, contraction of the capsule canbe treated by capsulectomy where both the implant and the capsule areremoved, and a new implant is implanted in the patient. Avoiding theneed to perform these procedures would be preferable.

In addition to the problems associated with the rotation of breastimplants, movement of either type of breast implant is undesirablebecause it will produce an unnatural appearance of the breast. Despitemovement of breast implants being undesirable, it is still not unusual.In one study of 715 reconstruction patients, 71.5% of patients at 10years had undergone reoperation for implant malposition (O'Shaughnessy,2015, Evolution and update on current devices for prosthetic breastreconstruction, Gland Surgery, 4(2):97-110). Displacements of an implantcan occur if the shape of the pocket for the implant is not precise, andphysical activity can also result in implant displacement. Movement ofan implant can also occur if supporting tissues around the implantstretch or become thinner, or if there is a loss of elasticity of thetissues. These conditions can, for example, result in “bottoming out”where the implant moves lower resulting in an unattractive appearance(see, Slavin, 2012, The use of acellular dermal matrices in revisionalbreast reconstruction, Plast. Reconstr. Surg. 130 (Suppl. 2): 70S-85S).These conditions can also result in the implant pocket stretchinglaterally causing the patient's breast implants to move sideways towardstheir sides or arm pits, particularly when lying down.

Various implantable devices have been developed to create pockets forbreast implants or for use as slings in breast reconstruction. Acelluardermal matrix (ADM), for example, has been used to cover tissueexpanders (Bertozzi, N. Ann Med Surg. 21:34-44 (2017)). In a typicalprocedure, the pectoralis major muscle is mobilized, and the ADM isattached to the edge of the muscle in order to create a sling andsubmuscular pocket for the tissue expander. The use of ADM eliminatesthe need to release and elevate the serratus anterior muscle, thepectoralis minor muscle, and the rectus abdominis fascia, andconsequently reduces postoperative pain. Such devices, however, are notdesigned to limit rotation of breast implants.

U.S. Pat. No. 4,936,858 to O'Keefe also discloses pouches for breastimplants, made from non-biodegradable yarn. The diameters of the pouchesexceed that of the implant by approximately 20%. The pouches are notdesigned to limit rotation of the breast implants.

U.S. Pat. No. 7,520,896 to Benslimane shows a breast implant with asupport element (5) attached to the breast implant using adhesive (4),and a securing element (3) connected to the support element. The supportelement (5) can be attached to the patient's pectoral muscle or in thearea of the axilla. FIG. 5 of Benslimane shows a breast implant thatcomprises two packages, an outer package and an inner package designedto prevent contamination of the breast implant by microbes. The outerpackage is non-sterile. The pouch, however, is not designed to limitrotation or migration of any breast implant, and is not designed forimplantation since the outer package is non-sterile.

U.S. Patent Application No. 20070196421 to Hunter discloses sleeves forbreast implants that comprise fibrosis-inhibiting drugs, but does notdisclose sleeves that are designed to limit rotation of breast implants.

U.S. Patent Application No. 20080128315 to Buevich discloses resorbablepouches for implantable medical devices, but does not disclose pouchesfor breast implants, or pouches designed to limit rotation of breastimplants.

U.S. Patent Application No. 20020165596 to Wilson discloses resorbablepouches for placement of bone graft or bone graft substitutes, but doesnot discloses pouches for breast implants, or pouches designed to limitrotation of breast implants.

U.S. Pat. No. 5,383,929 to Ledergerber discloses coverings for implantsthat disorganize scar tissue at the implant/body interface. Thecoverings are preferably made from expanded PTFE, a non-degradablepolymer.

WO2019/094861 to Mlodinow discloses mesh pouches for securing implantswithin a patient's body. The mesh pouches may be used to support abreast implant.

Notwithstanding the above, there is still a need for devices asdescribed herein that can limit not only rotation of breast implants,but also the movement of breast implants. There is also a need for newbreast implants that have been designed specifically for use withmedical devices that limit their ability to rotate in vivo. There is yetanother need to develop breast implant fixation devices that not onlylimit movement of breast implants, but prevent the breast implant frombeing palpable, or that hide any ripples or indentations in the breastresulting from implantation of breast implants.

SUMMARY OF THE INVENTION

Medical devices are described herein that limit the movement of breastimplants. In embodiments, pouches anchor in place in tissues at the siteof implantation, and will not migrate or rotate. Breast implants may beincorporated or inserted into the pouches, preferably prior toimplantation, limiting their ability to rotate or migrate. The pouchesmay also prevent the breast implants from being palpable, or prevent theformation of ripples or indentations on the skin following placement ofthe breast implants. The pouches limit rotation and migration of thebreast implants by applying compressive forces on the breast implants,allowing tissue in-growth into the pouches, or interlocking with thebreast implants, or combinations thereof. The interlocking mechanismprovides a physical barrier to the rotation or migration of the breastimplants when inserted in the pouches. The breast implants may be fullyor partially encased by the pouches. The pouches eliminate the problemof palpability or formation of skin indentations and ripples byproviding a thick layer on the front of the pouch that sits between thepatient's skin and the breast implant.

New breast implants for use with the pouches are also described. The newbreast implants have features that are designed to interlock with themedical devices so that rotation or migration of the breast implants islimited when implanted with the pouches. The interlocking mechanismprovides a physical barrier to the rotation or migration of the newbreast implants when inserted in the pouches. In embodiments, a fixationmeans mechanically secures the breast implant to the pouch. The newbreast implants may comprise tabs or other features that interlock withthe pouches to prevent rotation. Interlocking provides a physicalbarrier to limit rotation or migration of the new breast implants.

Methods to prepare the pouches and new breast implants are alsodescribed. The pouches are preferably made with absorbable polymers,most preferably with poly-4-hydroxybutyrate (P4HB) and copolymersthereof, or poly(butylene succinate) or copolymers thereof. The pouchesare preferably prepared with porosity that allows tissue in-growth, andanchoring of the pouches at the site of implantation. Preferably, thepouches are prepared with fibers, and most preferably with monofilamentfibers or dry spun fibers. Preferred methods of manufacturing thepouches include thermoforming, knitting, and dry spinning.

Also disclosed are methods of using the pouches with breast implants inbreast reconstruction, and breast augmentation, including augmentationmastopexy. The breast implants may be filled with either silicone orsaline. The pouches may be used following mastectomy in either one-stageor two-stage breast reconstruction procedures. In the latter case, apreferred method involves mobilizing the pectoralis major muscle,creating a submuscular pocket for a tissue expander (TE), optionally byattaching an acellular dermal matrix, P4HB textile or textile comprisingpolybutylene succinate or copolymer thereof to the elevated pectoralismajor muscle, inflating the TE, removing the TE, and implanting thepouch containing a breast implant in the submuscular pocket.

In breast augmentation procedures, the pouch containing a breast implantmay be placed in a breast pocket created either in the subglandularposition (above the pectoral muscle) or in the submuscular position(below the pectoral muscle). When used in breast augmentation, the pouchand breast implant may be inserted using transaxillary or transumbilicalmethods, or following a peri-areolar incision or incision at theinframammary fold (IMF).

A pouch for a breast implant to hold and prevent rotation of the breastimplant in a patient comprises a front sheet and a back sheet joined tothe front sheet along a medial edge and a lateral edge. Each of thefront sheet and back sheet are made of a material comprising a pluralityof pores for tissue ingrowth. The pouch further comprises at least oneseam spanning the medial edge to the lateral edge thereby forming acavity wherein the size and shape of the cavity is adapted to enclosethe breast implant. The seam has a curvature and is located relative tothe medial edge and the lateral edge to create an increased tensionforce on the breast implant in the vicinity of the seam serving tofirmly hold and prevent rotation of the breast implant within thecavity.

In embodiments, the seam is located in the lower region of the pouch andcomprises a concave curvature.

In embodiments, the pouch further comprises a second seam in the upperregion and the second seam has a convex curvature.

In embodiments, the first seam and the second seam are formed byknitting or welding.

In embodiments, the pouch further comprises a slit on the back sheet toprovide access to the cavity for the breast implant.

In embodiments, the pouch is formed of an elastic material and thecavity is undersized relative to the breast implant such that the cavityis elastically expanded when the breast implant is inserted therein.

In embodiments, the pouch comprises an auxetic structure, and in aparticular embodiment is an auxetic mesh.

In embodiments, the pouch further comprises a non-woven coating on thefront sheet where the NAC is to contact.

In embodiments, the pouch comprises a first substantially planar 2Dconfiguration, and a second 3D configuration when the breast implant isdisposed in the cavity.

In embodiments, the back sheet comprises a smooth alignment protrusionadapted to atraumatically and locally deform the breast implant therebyprohibiting the breast implant from rotating relative to the pouch insitu. The smooth alignment protrusion may be made of (or comprise) thesame material that the sheets are made from.

In embodiments, the pouch further comprises a mesh extension regionextending outwardly from the at least one seam. The mesh extensionregion may comprise a plurality of discrete tabs.

In another embodiment, a pouch of a breast implant fixation devicecomprises a back for placement on the chest wall of the patient, a frontbottom for placement in the lower pole of the breast, a front top forplacement in the upper pole of the breast, and a front intermediateregion between the front top and the front bottom for placement underthe skin of the patient; and is porous in order to allow tissuein-growth and limit movement of the breast implant.

In embodiments, the pouch comprises a slit or opening on the back toallow insertion of the breast implant into the pouch.

In embodiments, the front of the pouch of the breast implant fixationdevice is thicker than the back of the pouch.

In embodiments, the elasticity of the front of the pouch of the breastimplant fixation device is higher than the elasticity of the back of thepouch. The elasticity of the pouch makes is easy to insert the breastimplant in the pouch, and provides a tight conformation around thebreast implant.

In embodiments, one of the mechanical properties selected from the groupconsisting of porosity, thickness, and elasticity vary along the frontarea of the pouch from the top to the bottom. In a particularembodiment, the thickness decreases in the front of the pouch from thetop to the bottom.

In embodiments, the porosity of the pouch is adjusted to facilitatewrapping the breast implant in the pouch, particularly when the breastimplant is round. Varying the pore sizes in different regions of thepouch provides the pouch with different properties in the correspondingregions (namely, the front, back, bottom and top of the pouch). Inembodiments, a device includes larger pores in the back of the pouch toprovide a less dense pouch that is more drapable.

In embodiments, a device includes smaller pores in the front of thepouch to increase the surface area of the front of the pouch relative tothe back of the pouch, and to increase the surface area that is able tohold fat. In embodiments, fat is applied to the front of the pouch, andin a particular embodiment, autologous fat is applied or otherwiseprovided on the front of the pouch prior to implantation.

In embodiments, a flexible breast implant fixation device to preventmigration of the breast implant comprises a pouch shaped to cover thebreast implant wherein the pouch is adapted to engage the breast implantpreventing the breast implant from substantially rotating inside thepouch; and wherein the pouch further comprises a plurality of outwardlyextending (or protruding) anchors, and wherein the anchors arecharacterized by fibrous or filament-type construction, and optionally,wherein the density of the anchors ranges from 10-50 anchors per squarecm, and optionally, 20-30 anchors per square cm.

In view of the foregoing, it is thus an object of the invention toprovide medical devices, e.g., pouches, for use with breast implantsthat limit movement, including rotation or migration, of the breastimplants.

It is another object of the invention to provide new breast implantswith features that limit their movement in vivo, including rotation,when used with the pouches.

It is still another object of the invention to provide breast implantfixation devices that not only limit migration of breast implants, butprevent the breast implant from being palpable, or that prevent theformation of any ripples or indentations when breast implants are placedin the breasts.

It is yet another object of the invention to provide methods to prepareor manufacture pouches that limit movement of breast implants, andmethods to prepare new breast implants with features that limit theirmovement in vivo.

It is still another object of the invention to provide methods toimplant the pouches and breast implants.

These and other objects, aspects, and advantages of the subjectinvention shall become apparent in view of the following descriptionwith reference to the accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an isometric view of an implantable pouch in accordance withan embodiment of the invention including a slit for insertion of abreast implant and a tightenable draw cord serving to apply pressure onthe breast implant and limit its rotation or migration afterimplantation.

FIG. 2A shows the front half of the breast implant pouch used to preparethe implant shown in FIG. 1 comprising a circular mesh with rectangularholes cut in the mesh around its perimeter.

FIG. 2B shows the back half of the breast implant pouch used to preparethe pouch implant shown in FIG. 1 comprising a circular mesh with a sealarea for bonding with the front half of the breast implant pouch shownin FIG. 2A.

FIG. 3 is a cross-sectional view of the pouch shown in FIG. 1 , with thebreast implant inside the pouch, and part of the draw cord shown at thebase of the pouch.

FIGS. 4A, 4B are isometric views of a pouch in accordance with anotherembodiment of the invention having four slots, with tabs from a breastimplant located inside the pouch protruding through the slots.

FIG. 5 is a diagram illustrating solution spinning equipment used toprepare a dry spun pouch in accordance with an embodiment of theinvention.

FIG. 6 is a cross-sectional view of the pouch shown in FIGS. 4A, 4B,containing a tabbed breast implant with the tabs of the breast implantprotruding from the breast implant through slots in the pouch inaccordance with another embodiment of the invention.

FIG. 7 shows the back of a pouch for a breast implant including aV-shape slit in the back for insertion of the breast implant, and foursmall suture straps placed at 90 degree intervals around the pouchperimeter in accordance with another embodiment of the invention.

FIG. 8 is a diagram showing the loop knit pattern of a pouch for abreast implant in accordance with an embodiment of the invention, formedby knitting a front fabric and a back fabric separately, except at thetwo edges 404 where the fabric is knit simultaneously to join the frontand back fabrics, and in the connected area 412 where the fabric is alsoknitted simultaneously to join the front and back fabrics with an openand closed stitch knit.

FIG. 9 shows a pouch formed from a tubular warp knitted structure inaccordance with an embodiment of the invention.

FIG. 10 shows a breast implant in a pouch formed from a warp knittedmesh structure of poly-4-hydroxybutyrate fiber in accordance with anembodiment of the invention including a knitted seal at one end thatpermits uniform stretching of the pouch.

FIG. 11A shows a spacer mesh with a honey comb knit pattern for use infabricating an implant breast fixation device in accordance with anembodiment of the invention.

FIG. 11B is a side view of the breast implant fixation pouch deviceshown in FIG. 11A.

FIG. 12A is a diagram showing the position and length of a slit made ina spacer mesh, such as that shown in FIG. 11A, during the preparation ofa breast implant fixation pouch device.

FIG. 12B depicts a spacer mesh including a slit in accordance with anembodiment of the invention used in the preparation of a breast implantfixation pouch device.

FIG. 13A depicts a spacer fabric that is cut to separate the front andback faces of a spacer mesh during the manufacture of a breast implantfixation pouch device in accordance with an embodiment of the invention.

FIG. 13B is an enlarged view of the cut spacer fabric depicted in FIG.13A in accordance with an embodiment of the invention.

FIG. 14 is a figure of a breast implant fixation pouch formed from aspacer mesh by cutting the internal connecting fibers in the midplaneregion between the front and back faces of the spacer mesh (asillustrated in FIG. 13A), and flipping the construct inside-out to forma self-gripping pouch for a breast implant with fibers exposed as tissueanchors on the outer surface of the pouch in accordance with anembodiment of the invention.

FIG. 15 is a diagram showing a process to construct a breast implantfixation pouch from two semicircular meshes and a round mesh by sewingthe pieces together along the indicated stitch lines in accordance withan embodiment of the invention.

FIG. 16A depicts the stitched edge of a breast implant fixation pouchconstructed as shown in FIG. 15 .

FIG. 16B is a diagram showing the stitch pattern used to stitch the edgeof the breast implant fixation pouch constructed in FIG. 16A.

FIG. 17A shows the front of a breast implant fixation pouch,manufactured as shown in FIG. 15 , with a breast implant insertedtherein in accordance with an embodiment of the invention.

FIG. 17B shows the back of a breast implant fixation pouch, manufacturedas shown in FIG. 15 , with a breast implant inserted therein inaccordance with an embodiment of the invention.

FIG. 18 is a diagram showing three round meshes pre-assembled togetherto produce an enhanced front mesh of a breast implant pouch inaccordance with an embodiment of the invention.

FIGS. 19A, 19B are back perspective and side views, respectively, of apouch for holding an implant in accordance with an embodiment of theinvention.

FIG. 19C is a cross sectional view of the pouch shown in FIG. 19B takenalong line 19C-19C in situ, and illustrating the front of the pouchhaving a greater thickness than the back of the pouch.

FIG. 20 is a cross sectional view of another pouch in situ for holdingan implant illustrating the front of the pouch having a thickness thatvaries from the top of the pouch to the bottom of the pouch inaccordance with an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

Before the present invention is described in detail, it is to beunderstood that this invention is not limited to particular variationsset forth herein as various changes or modifications may be made to theinvention described and equivalents may be substituted without departingfrom the spirit and scope of the invention. As will be apparent to thoseof skill in the art upon reading this disclosure, each of the individualembodiments described and illustrated herein has discrete components andfeatures which may be readily separated from or combined with thefeatures of any of the other several embodiments without departing fromthe scope or spirit of the present invention. In addition, manymodifications may be made to adapt a particular situation, material,composition of matter, process, process act(s) or step(s) to theobjective(s), spirit or scope of the present invention. All suchmodifications are intended to be within the scope of the claims madeherein.

Methods recited herein may be carried out in any order of the recitedevents which is logically possible, as well as the recited order ofevents. Furthermore, where a range of values is provided, it isunderstood that every intervening value, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range is encompassed within the invention. Also, it iscontemplated that any optional feature of the inventive variationsdescribed may be set forth and claimed independently, or in combinationwith any one or more of the features described herein.

All existing subject matter mentioned herein (e.g., publications,patents, patent applications and hardware) is incorporated by referenceherein in its entirety except insofar as the subject matter may conflictwith that of the present invention (in which case what is present hereinshall prevail).

Reference to a singular item, includes the possibility that there areplural of the same items present. More specifically, as used herein andin the appended claims, the singular forms “a,” “an,” “said” and “the”include plural referents unless the context clearly dictates otherwise.It is further noted that the claims may be drafted to exclude anyoptional element. As such, this statement is intended to serve asantecedent basis for use of such exclusive terminology as “solely,”“only” and the like in connection with the recitation of claim elements,or use of a “negative” limitation. Last, it is to be appreciated thatunless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs.

In embodiments of the invention, an implantable medical device for thesurgeon limits rotation or migration of a breast implant, maintains thepatient's physical appearance, and decreases the chances of capsularcontraction and the development of breast-implant associated lymphoma.The medical device used to prevent migration and rotation of a breastimplant can be made for use with a wide variety of types of breastimplants, and used in breast reconstruction procedures followingmastectomy as well as breast augmentation procedures, includingaugmentation mastopexy procedures.

In embodiments, the medical device is a pouch, and is utilized byinserting the breast implant inside the pouch and securing the breastimplant inside the pouch so it is unable to rotate inside the pouch.Preferably, the breast implant cannot rotate more than 45 degrees insidethe pouch, and more preferably the breast implant cannot rotate morethan 30 degrees inside the pouch. After securing the breast implantinside the pouch, the pouch containing the breast implant is thenimplanted in the breast by the surgeon. Rotation and migration of thebreast implant is prevented after implantation by tissue growth into thepouch which anchors the pouch and therefore the breast implant in place.Preferably, the pouch is made from synthetic polymeric material toreduce the risk of disease transmission associated with human oranimal-derived implants.

In embodiments, the medical device is a breast implant fixation devicecomprising a pouch, and is utilized by inserting the breast implant inthe pouch. The pouch is porous and allows tissue in-growth. Tissuein-growth fixates the pouch in place and prevents migration of thebreast implant. Palpability of the breast implant is reduced oreliminated by the enhanced or optimized thickness of the front of thepouch which separates the patient's skin and the breast implant. Theenhanced or optimized thickness of the front of the pouch also reducesor eliminates the appearance of indentations or ripples on the patientsskin due to the presence of the breast implant.

I. Definitions

“Absorbable” as generally used herein means the material is degraded inthe body, and the degradation products are eliminated or excreted fromthe body. The terms “absorbable”, “resorbable”, “degradable”, and“erodible”, with or without the prefix “bio”, can be usedinterchangeably herein, to describe materials broken down and graduallyabsorbed, excreted, or eliminated by the body.

“Average pore size diameter” as used herein is calculated using opensource ImageJ software available athttps://imagej.nih.gov/ij/index.html.

“Bioactive agent” is used herein to refer to therapeutic, prophylacticor diagnostic agents, preferably agents that promote healing and theregeneration of host tissue, and also therapeutic agents that prevent,inhibit or eliminate infection. “Agent” includes a single such agent andis also intended to include a plurality.

“Biocompatible” as generally used herein means the biological responseto the material or device being appropriate for the device's intendedapplication in vivo. Any metabolites of these materials should also bebiocompatible.

“Blend” as generally used herein means a physical combination ofdifferent polymers, as opposed to a copolymer formed of two or moredifferent monomers.

“Breast implant” as used herein refers to a prosthesis that is implantedin place of a female breast, but can also be implanted to change thesize, shape and contour of a woman's breast.

“Burst strength” as used herein is determined by test method ASTMD6797-02 “Standard test method for bursting strength of fabrics constantrate of extension (CRE) ball burst test,” using a MTS Q-Test Eliteuniversal testing machine or similar device. The testing fixture uses a⅜ inch diameter ball.

“Copolymers of poly(butylene succinate)” as generally used herein meansany polymer containing 1,4-butanediol units and succinic acid units withone or more different diols, diacid or hydroxycarboxylic acid units,including hydroxycarboxylic acid groups with one or more carboxylic acidor hydroxy acid groups. The copolymers may also comprise chainextenders, coupling agents, cross-linking agents or branching agents.

“Copolymers of poly-4-hydroxybutyrate” as generally used herein meansany polymer containing 4-hydroxybutyrate with one or more differenthydroxy acid units.

“Elongation to break” as used herein means the increase in length of amaterial that occurs when tension is applied to break the material. Itis expressed as a percentage of the material's original length.

“Endotoxin units” as used herein are determined using the limulusamebocyte lysate (LAL) assay as further described by Gorbet et atBiomaterials, 26:6811-6817 (2005).

“Inframammary fold” or “IMF” as generally used herein is the positionwhere the lower pole of the breast meets the chest wall.

“Lower pole” as generally used herein means the part of the breastlocated between the inframammary fold (IMF) and the nipple meridianreference, and protruding away from the chest wall.

“Macro-porous” materials or structures as used herein have average poresize diameters of at least 25 microns, more preferably at least 50microns, and even more preferably at least 75 microns.

“Molecular weight” as used herein, unless otherwise specified, refers tothe weight average molecular weight (Mw), not the number averagemolecular weight (Mn), and is measured by GPC relative to polystyrene.

“Nipple meridian reference” or “NMR” is the plane drawn horizontallythrough the nipple to the chest wall.

“Oriented” as generally used herein refers to molecular alignment ofpolymer chains in a material. A polymer that has been stretched becomespartly oriented and then highly oriented, and the tensile strengthincreases with increasing orientation. For example, an unorientedpolymeric fiber may be stretched to orient the fiber which results in apolymeric fiber with higher tensile strength. An “oriented mesh” means amesh made with oriented fibers.

“Poly-4-hydroxybutyrate” as generally used herein means a homopolymercontaining 4-hydroxybutyrate units. It can be referred to herein asTepha's P4HB™ polymer or TephaFLEX® biomaterial (manufactured by Tepha,Inc., Lexington, MA).

“Poly(butylene succinate)” as generally used herein means a polymercontaining 1,4-butanediol units and succinic acid units.

“Strength retention” as used herein means the amount of time that amaterial maintains a particular mechanical property followingimplantation or exposure to a particular set of conditions. For example,if the stress required to break a multifilament yarn or monofilamentfiber after one month is half of its original value then themultifilament or monofilament fiber is said to have a 50% strengthretention after one month.

“Suture pullout strength” as used herein means the peak load (kg) atwhich a breast implant fixation device fails to retain a suture. It isdetermined using a tensile testing machine by securing the breastimplant fixation device in a horizontal plate, threading a suture in aloop through the breast implant fixation device at a distance of 1 cmfrom the edge of the breast implant fixation device, and securing thesuture arms in a fiber grip positioned above the breast implant fixationdevice. Testing is performed at a crosshead rate of 100 mm/min, and thepeak load (kg) is recorded. The suture is selected so that the breastimplant fixation device will fail before the suture fails. The suturepullout strength may be converted and expressed as Newtons.

“Tensile modulus” is the ratio of stress to strain for a given materialwithin its proportional limit.

“Tissue expander” (“TE”) as used herein means a breast implant that isplaced temporarily in the breast to expand tissues and make room for abreast implant. The TE is expanded (e.g., inflated) periodically, forexample, by injecting a liquid or gas into the TE. The TE is removedonce the tissue has been sufficiently stretched to make room for apermanent breast implant.

“Upper pole” as generally used herein means the top part of the breastlocated between the nipple meridian reference and the position at thetop of the breast where the breast takes off from the chest wall, andprotruding away from the chest wall.

II. Materials for Preparing Pouches to Limit Movement of Breast Implants

In accordance with embodiments of the invention described herein,implantable medical devices limit the movement of breast implants. Inparticular embodiments, the medical devices are in the form of a pouchsized to enclose the breast implant. In embodiments, the pouches areporous, and fixated in place by tissue in-growth. The pouches anchor atthe site of implantation, and in embodiments limit movement of thebreast implants by applying compressive or frictional forces to thebreast implants, or interlocking with the breast implants. Inembodiments, the pouches prevent the breast implants from rotatinginside the pouches. In embodiments, the pouches anchor at the site ofimplantation, and prevent pocket stretch, lateral displacement of theimplant, and ptosis by preventing or limiting migration of the breastimplant.

With reference to FIGS. 19A-19C, an embodiment of a pouch 900 inaccordance with the subject invention is shown. As described furtherherein, the pouch 900 is preferably porous and has a back 910 forplacement on the chest wall of the patient, and a front 920 forplacement under the skin 932 of the patient. In embodiments, the front920 of the pouch has a thickness (t) sufficient to hide any ripples orindentations in the patient's skin when a breast implant 934 is placedin the pouch, and the pouch is placed in the patient's breast. Thethickness (t) of the pouch is also preferably sufficient to prevent thebreast implant from being palpable. An exemplary range for the thickness(t) on the front face is 0.5-10 mm and more preferably from 0.5-3 mm, or0.75-3 mm. In embodiments, the front of the pouch has a thickness toprevent palpability and the appearance of ripples or indentations on thepatient's skin. In the embodiment shown in FIG. 19C, the thickness (t)of the front 920 of the pouch is uniform from the top 924 to the bottom922. Additionally, the front 920 of the pouch can be thicker than theback 910 of the pouch. The thickness of the front 920 may be a factor of2 to 5 times greater than the thickness of the back of the pouch. Inembodiments, the thickness of the back of pouch ranges from 0.2-0.4 mm.

However, in other embodiments, the thickness of the pouch or othermechanical properties described herein vary along the front of the pouchfrom the top 924 to the bottom 922, or otherwise. In the embodimentshown in FIG. 20 , for example, the thickness decreases along the pouchfrom the top to the bottom. The front top 924 (t_(top)) may have athickness of 5-10 times greater than the front bottom 922 (t_(bottom)).Additionally, in a preferred embodiment, the back 910 has a thicknessless than the front.

The elasticity may also vary along the regions of the pouch. Inembodiments, a pouch has a back 910 for placement on the chest wall ofthe patient, and a front 920 for placement under the skin 932 of thepatient, and an elasticity of the front area 932 of the pouch of 15-75%,and more preferably 30-65%, and an elasticity of the back area 910 ofthe pouch of 5-25%, and more preferably 8-20%, when the elasticities aremeasured as the percent increases of the areas when the areas aresubject to deformation in ASTM burst method D6797-02 using a round ball.In a particularly preferred embodiment, the elasticity of the front areais 30-65%, and the elasticity of the back area is 5-25%. Theelasticities of the front and back areas allow the breast implant 934 tobe easily inserted in the pouch with the pouch conforming tightly to thecontours of the breast implant.

In embodiments, the pouches for the breast implants have differentporosities in different regions 910, 920 of the pouch, or differentamongst front regions 922, 924 and an intermediate spanning from thefront bottom region 922 to front top region 924.

In embodiments, with reference to FIG. 19C, a pouch has large averagepore size diameters on the back 910 of the pouch and around theperimeter of the pouch to improve the drapability of the breast implant,and smaller average pore size diameters on the front top 924 of thepouch (which is placed in the front upper pole 938 of the breast) toincrease the surface area available for holding fat graft. Inembodiments, the front superior area 924 of the pouch is more dense thanthe back of the pouch.

In embodiments, the fixation devices prohibit rotation of the envelopedbreast implant by more than 45 degrees, and more preferably by more than30 degrees. In embodiments, the pouches prevent migration of the breastimplants by more than 5 cm. The pouches partially or completely coverthe breast implants. Preferably the breast implants are inserted insidethe pouches prior to implantation. The pouches are preferably porous,and allow tissue in-growth. The dimensions of the pouches are tailoredto accommodate the size and shape of the breast implant being implanted.The dimensions of the breast implants are selected by the surgeonaccording to the needs of the patient, and the patient's preferences.

The pouches are preferably made of absorbable polymers. Additionally,the pouches may be made from a single component, such as an unoriented,partially or fully oriented monofilament fiber or fibers, includingnonwovens and knitted mesh, or from two or more components, such asfibers, textiles or films with different properties. The pouches canoptionally comprise bioactive agents, as well as cells, including stemcells. The pouches so formed preferably have a pyrogen level of lessthan 20 endotoxin units per device, and can be sterilized.

A. Polymers for Preparing Pouches

The pouches may comprise degradable materials, and more preferably aremade completely from degradable materials. In a preferred embodiment,the devices for fixation of breast implants are made from one or moreabsorbable polymers, preferably absorbable thermoplastic polymers andcopolymers. The implantable pouch may, for example, be prepared frompolymers including, but not limited to, polymers of glycolic acid,lactic acid, 1,4-dioxanone, trimethylene carbonate, 3-hydroxybutyricacid, 4-hydroxybutyrate, ε-caprolactone, 1,4-butanediol, and succinicacid, including polyglycolic acid, polylactic acid, polydioxanone,polycaprolactone, copolymers of glycolic and lactic acids, such asVICRYL® polymer, MAXON® and MONOCRYL® polymers, and includingpoly(lactide-co-caprolactones); poly(orthoesters); polyanhydrides;poly(phosphazenes); polyhydroxyalkanoates (PHA's); synthetically orbiologically prepared polyesters; polycarbonates; tyrosinepolycarbonates; polyamides (including synthetic and natural polyamides,polypeptides, and poly(amino acids)); polyesteramides; poly(alkylenealkylates); polyethers (such as polyethylene glycol, PEG, andpolyethylene oxide, PEO); polyvinyl pyrrolidones or PVP; polyurethanes;polyetheresters; polyacetals; polycyanoacrylates;poly(oxyethylene)/poly(oxypropylene) copolymers; polyacetals,polyketals; polyphosphates; (phosphorous-containing) polymers;polyphosphoesters; polyalkylene oxalates; polyalkylene succinates;poly(maleic acids); silk (including recombinant silks and silkderivatives and analogs); chitin; chitosan; modified chitosan;biocompatible polysaccharides; hydrophilic or water soluble polymers,such as polyethylene glycol, (PEG) or polyvinyl pyrrolidone (PVP), withblocks of other biocompatible or biodegradable polymers, for example,poly(lactide), poly(lactide-co-glycolide, or polycaprolactone andcopolymers thereof, including random copolymers and block copolymersthereof. Preferably the absorbable polymer or copolymer will besubstantially or completely resorbed two years after implantation.

Blends of polymers, preferably absorbable polymers, can also be used toprepare the pouches. Particularly preferred blends of absorbablepolymers include, but are not limited to, polymers of glycolic acid,lactic acid, 1,4-dioxanone, trimethylene carbonate, 3-hydroxybutyricacid, 4-hydroxybutyric acid, ε-caprolactone, 1,4-butanediol, succinicacid or copolymers thereof.

In a particularly preferred embodiment, the pouches comprisepoly-4-hydroxybutyrate (Tepha's P4HB™ polymer, Lexington, MA) or acopolymer thereof, and may in one embodiment be made completely withP4HB or copolymer thereof. Copolymers include P4HB with anotherhydroxyacid, such as 3-hydroxybutyrate, and P4HB with glycolic acid orlactic acid monomer. P4HB is a strong, pliable thermoplastic polyesterthat is biocompatible and resorbable (Williams, et al.Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medicaldevices for tissue repair and regeneration, Biomed. Tech. 58(5):439-452(2013)). Upon implantation, P4HB hydrolyzes to its monomer, and themonomer is metabolized via the Krebs cycle to carbon dioxide and water.In a preferred embodiment, the P4HB homopolymer and copolymers thereofhave a weight average molecular weight, Mw, within the range of 50 kDato 1,200 kDa (by GPC relative to polystyrene) and more preferably from100 kDa to 600 kDa. A weight average molecular weight of the polymer of50 kDa or higher is preferred for processing and mechanical properties.

In another preferred embodiment, the pouches comprise a polymercomprising at least a diol and a diacid. In a particularly preferredembodiment, the polymer used to prepare the pouch is poly(butylenesuccinate) (PBS) wherein the diol is 1,4-butanediol and the diacid issuccinic acid. The poly(butylene succinate) polymer may be a copolymerwith other dials, other diacids or a combination thereof. For example,the polymer may be a poly(butylene succinate) copolymer that furthercomprises one or more of the following: 1,3-propanediol, 2,3-butanediol,ethylene glycol, 1,5-pentanediol, glutaric acid, adipic acid,terephthalic acid, malonic acid, methylsuccinic acid, dimethylsuccinicacid, and oxalic acid. Examples of preferred copolymers are:poly(butylene succinate-co-adipate), poly(butylenesuccinate-co-terephthalate), poly(butylene succinate-co-butylenemethylsuccinate), poly(butylene succinate-co-butylenedimethylsuccinate), poly(butylene succinate-co-ethylene succinate) andpoly(butylene succinate-co-propylene succinate). The poly(butylenesuccinate) polymer or copolymer may also further comprise one or more ofthe following: chain extender, coupling agent, cross-linking agent andbranching agent. For example, poly(butylene succinate) or copolymerthereof may be branched, chain extended, or cross-linked by adding oneor more of the following agents: malic acid, trimethylol propane,trimesic acid, citric acid, glycerol propoxylate, and tartaric acid.Particularly preferred agents for branching, chain extension, orcrosslinking the poly(butylene succinate) polymer or copolymer thereofare hydroxycarboxylic acid units. Preferably the hydroxycarboxylic acidunit has two carboxylic groups and one hydroxyl group, two hydroxylgroups and one carboxyl group, three carboxyl groups and one hydroxylgroup, or two hydroxyl groups and two carboxyl groups. In one preferredembodiment, the pouch comprises poly(butylene succinate) comprisingmalic acid as a branching, chain extending, or cross-finking agent. Thispolymer may be referred to as poly(butylene succinate) cross-linked orchain-extended with malic acid, succinic acid-1,4-butanediol-malic acidcopolyester, or poly(1,4-butylene glycol-co-succinic acid), cross-linkedor chain-extended with malic acid. It should be understood thatreferences to malic acid and other cross-linking agents, couplingagents, branching agents and chain extenders include polymers preparedwith these agents wherein the agent has undergone further reactionduring processing. For example, the agent may undergo dehydration duringpolymerization. Thus, poly(butylene succinate)-malic acid copolymerrefers to a copolymer prepared from succinic acid, 1,4-butanediol andmalic acid. In another preferred embodiment, malic acid may be used as abranching, chain-extending or cross-linking agent to prepare a copolymerof poly(butylene succinate) with adipate, which may be referred to aspoly[(butylene succinate)-co-adipate] cross-linked or chain-extendedwith malic acid. As used herein, “poly(butylene succinate) andcopolymers” includes polymers and copolymers prepared with one or moreof the following: chain extenders, coupling agents, cross-linking agentsand branching agents. In a particularly preferred embodiment, thepoly(butylene succinate) and copolymers thereof contain at least 70%,more preferably 80%, and even more preferably 90% by weight of succinicacid and 1,4-butanediol units. The polymers comprising diacid and diols,including poly(butylene succinate) and copolymers thereof and othersdescribed herein, preferably have a weight average molecular weight (Mw)of 10,000 to 400,000, more preferably 50,000 to 300,000 and even morepreferably 100,000 to 200,000 based on gel permeation chromatography(GPC) relative to polystyrene standards. In a particularly preferredembodiment, the polymers and copolymers have a weight average molecularweight of 50,000 to 300,000, and more preferably 75,000 to 300,000. Inone preferred embodiment, the poly(butylene succinate) or copolymerthereof used to make the pouch, or a component of the pouch, has one ormore, or all of the following properties: density of 1.23-1.26 g/cm³,glass transition temperature of −31° C. to −35° C., melting point of113° C. to 117° C., melt flow rate (MFR) at 190° C./2.16 kgf of 2 to 10g/10 min, and tensile strength of 30 to 60 MPa.

B. Additives

Certain additives may be incorporated into the pouches, preferably inthe absorbable polymer, copolymer or blends thereof that are used tomake the pouch. Preferably, these additives are incorporated during acompounding process to produce pellets that can be subsequentlymelt-processed. For example, pellets may be extruded into fiberssuitable for making the pouches. In another embodiment, the additivesmay be incorporated using a solution-based process, for example, fibersmay be spun from solutions of the polymer and one or more additives. Ina preferred embodiment, the additives are biocompatible, and even morepreferably the additives are both biocompatible and resorbable.

In one embodiment, the additives may be nucleating agents and/orplasticizers. These additives may be added in sufficient quantity toproduce the desired result. In general, these additives may be added inamounts between 1% and 20% by weight. Nucleating agents may beincorporated to increase the rate of crystallization of the polymer,copolymer or blend. Such agents may be used, for example, to facilitatefabrication of the pouch, and to improve the mechanical properties ofthe pouch. Preferred nucleating agents include, but are not limited to,salts of organic acids such as calcium citrate, polymers or oligomers ofPHA polymers and copolymers, high melting polymers such as PGA, talc,micronized mica, calcium carbonate, ammonium chloride, and aromaticamino acids such as tyrosine and phenylalanine.

Plasticizers that may be incorporated into the compositions forpreparing the pouches include, but are not limited to, di-n-butylmaleate, methyl laureate, dibutyl fumarate, di(2-ethylhexyl) (dioctyl)maleate, paraffin, dodecanol, olive oil, soybean oil, polytetramethyleneglycols, methyl oleate, n-propyl oleate, tetrahydrofurfuryl oleate,epoxidized linseed oil, 2-ethyl hexyl epoxytallate, glycerol triacetate,methyl linoleate, dibutyl fumarate, methyl acetyl ricinoleate, acetyltri(n-butyl) citrate, acetyl triethyl citrate, tri(n-butyl) citrate,triethyl citrate, bis(2-hydroxyethyl) dimerate, butyl ricinoleate,glyceryl tri-(acetyl ricinoleate), methyl ricinoleate, n-butyl acetylrincinoleate, propylene glycol ricinoleate, diethyl succinate,diisobutyl adipate, dimethyl azelate, di(n-hexyl) azelate, tri-butylphosphate, and mixtures thereof. Particularly preferred plasticizers arecitrate esters.

C. Bioactive Agents

The pouches can be loaded or coated with bioactive agents. Bioactiveagents may be included in the pouches for a variety of reasons. Forexample, bioactive agents may be included in order to improve tissuein-growth into the pouch, to improve tissue maturation, to provide forthe delivery of an active agent, to improve wettability of the implant,to prevent infection, and to improve cell attachment.

The pouches may contain cellular adhesion factors, including celladhesion polypeptides. As used herein, the term “cell adhesionpolypeptides” refers to compounds having at least two amino acids permolecule that are capable of binding cells via cell surface molecules.The cell adhesion polypeptides include any of the proteins of theextracellular matrix which are known to play a role in cell adhesion,including fibronectin, vitronectin, laminin, elastin, fibrinogen,collagen types I, II, and V, as well as synthetic peptides with similarcell adhesion properties. The cell adhesion polypeptides also includepeptides derived from any of the aforementioned proteins, includingfragments or sequences containing the binding domains.

The pouches can incorporate wetting agents designed to improve thewettability of the surfaces of the pouch to allow fluids to be easilyadsorbed onto the pouch surfaces, and to promote cell attachment and ormodify the water contact angle of the pouch surface. Examples of wettingagents include polymers of ethylene oxide and propylene oxide, such aspolyethylene oxide, polypropylene oxide, or copolymers of these, such asPLURONICS®. Other suitable wetting agents include surfactants oremulsifiers.

The pouches can contain gels, hydrogels or living hydrogel hybrids tofurther improve wetting properties and to promote cellular growththroughout the thickness of the scaffold. Hydrogel hybrids consist ofliving cells encapsulated in a biocompatible hydrogel like gelatin, silkgels, and hyaluronic acid (HA) gels.

The pouches can contain active agents designed to stimulate cellin-growth, including growth factors, cellular differentiating factors,cellular recruiting factors, cell receptors, cell-binding factors, cellsignaling molecules, such as cytokines, and molecules to promote cellmigration, cell division, cell proliferation and extracellular matrixdeposition. Such active agents include fibroblast growth factor (FGF),transforming growth factor (TGF), platelet derived growth factor (PDGF),epidermal growth factor (EGF), granulocyte-macrophage colony stimulationfactor (GMCSF), vascular endothelial growth factor (VEGF), insulin-likegrowth factor (IGF), hepatocyte growth factor (HGF), interleukin-1-B(IL-1 B), interleukin-8 (IL-8), and nerve growth factor (NGF), andcombinations thereof.

Other bioactive agents that can be incorporated in the pouches includeantimicrobial agents, in particular antibiotics, disinfectants,oncological agents, anti-scarring agents, anti-inflammatory agents,anesthetics, small molecule drugs, anti-angiogenic factors andpro-angiogenic factors, immunomodulatory agents, and blood clottingagents. The bioactive agents may be proteins such as collagen andantibodies, peptides, polysaccharides such as chitosan, alginate,hyaluronic acid and derivatives thereof, nucleic acid molecules, smallmolecular weight compounds such as steroids, inorganic materials such ashydroxyapatite, or complex mixtures such as platelet rich plasma.Suitable antimicrobial agents include: bacitracin, biguanide,trichlosan, gentamicin, minocycline, rifampin, vancomycin,cephalosporins, copper, zinc, silver, and gold. Nucleic acid moleculesmay include DNA, RNA, siRNA, miRNA, antisense or aptamers.

The pouches may also comprise allograft material and xenograftmaterials, including acellular dermal matrix material and smallintestinal submucosa (SIS).

In yet another preferred embodiment, the pouches may incorporate systemsfor the controlled release of the therapeutic or prophylactic agents.

D. Fibers

The pouches may comprise fibers. The fibers are preferably made fromdegradable thermoplastic polymers, and even more preferably fromdegradable thermoplastic polyesters. The fibers are preferably made fromthe degradable materials listed in section II.A above. In a preferredembodiment, the fibers are made from P4HB or copolymer thereof. Inanother preferred embodiment, the fibers are made from poly(butylenesuccinate) or copolymer thereof. The fibers maybe monofilament fibers,multifilament fibers, or combinations thereof. The fibers may be a yarnthat is twisted, not twisted, or substantially parallel strands. Thefibers may be unoriented, partially oriented, highly oriented orcombinations thereof. Preferably, the fibers are highly oriented. Thefibers may have elongation to break values of 3% to 1,100%, and morepreferably from 10% to 100%. The fibers may have diameters ranging from1 μm to 5 mm, more preferably from 10 μm to 1 mm, and even morepreferably from 20 μm to 750 μm. The fibers in the pouch may havedifferent weight average molecular weights. Preferably the polymers ofthe fibers have weight average molecular weights of 10 kDa to 1,200 kDa,but more preferably 50 kDa to 600 kDa. The fibers in the pouch may havedifferent tensile strengths. Preferably, the tensile strength of thefibers in the pouch is 300-1,300 MPa. The fibers in the pouch arepreferably flexible. Preferably, the fibers in the pouch have a tensilemodulus of 70-1,000 MPa, and more preferably 400-1,000 MPa. The fibersmay have short strength retention profiles, prolonged strength retentionprofiles, or combinations thereof. In one embodiment, a short strengthretention profile is 1 to 12 weeks, and a prolonged strength retentionprofile is 4 months to 5 years, more preferably 4 months to 2 years. Thefibers of the pouch may have different degradation rates in vivo. Somefibers may degrade quickly while other fibers may degrade slowly. Inanother embodiment, the fibers comprise an additive or bioactive agent.The fibers can be produced by any suitable method but melt extrusion orsolvent spinning are preferred.

In a preferred embodiment, the fiber is made from P4HB monofilamentfiber. Suitable P4HB monofilament filament fibers can be produced bymelt extrusion using the following method. Bulk P4HB resin in pelletform is dried to less than 300 ppm water using a rotary vane vacuum pumpsystem. The dried resin is transferred to an extruder feed hopper withnitrogen purge to keep the pellets dry. The pellets are gravity fed intoa chilled feeder section and introduced into the extruder barrel, whichis 1.50 inches (3.81 cm) in diameter and fitted with an extrusion screwwith a 30:1 L/D ratio. The extruder barrel contains 5 heating zones (orextrusion zones)—zones 1, 2, 3, 4 and 5. A suitable extruder ismanufactured by American Kuhne. The heated and softened resin from theextruder is fed into a heated metering pump (melt pump) and from themelt pump the extruded resin is fed into the heated block and aneight-hole spinneret assembly. Processing profile ranges from 40° C. to260° C. for temperatures, and 400 psi to 2000 psi for pressures, areused. The molten filaments are water quenched and conveyed into athree-stage orientation, with inline relaxation, before winding of themonofilaments on spools. Typical test values for extruded monofilamentfiber are shown in Table 1.

TABLE 1 Mechanical Test Data for P4HB Monofilament Breaking Diameter,Strength, Break mm Kgf Elongation 0.165 1.80 26% 0.150 1.80 30% 0.1001.00 29%

In another preferred embodiment, the fiber is made from poly(butylenesuccinate) or copolymer thereof. Suitable monofilament fibers ofpoly(butylene succinate) or copolymer thereof can be produced by meltextrusion.

Pouches that can prevent rotation and migration of breast implants canbe prepared from the fibers described above. Such pouches can beproduced from slow and fast degrading fibers, degradable fibers ofdifferent molecular weights, fibers that are unoriented, partiallyoriented and fully oriented, fibers with different elongation to breakvalues, tensile strengths and tensile modulus values, or combinationsthereof.

E. Films

The pouches may comprise films, and more preferably films that have beenperforated to make them porous. The pores of the perforated filmspreferably have pore diameters from 0.01 mm to 10 mm, and morepreferably from 0.1 mm to 1 mm. In a particularly preferred embodiment,the perforated films have pores that are larger than 0.5 mm, even morepreferably at least 0.8 mm. The density of the pores of the perforatedfilms is preferably greater than 1 per square cm, but less than 50 persquare cm. The films are preferably made from degradable thermoplastics,and even more preferably from degradable polyesters. The films arepreferably made from the degradable materials listed in Section II.Aabove. In a preferred embodiment, the films are made from P4HB orcopolymer thereof, or from poly(butylene succinate) or copolymerthereof. The weight average molecular weight of the polymers in thefilms is preferably 10 kDa to 1,200 kDa, but is more preferably 50 kDato 600 kDa. The films may be unoriented, partially oriented,mono-axially oriented or bi-axially oriented. The elongation to break ofthe films can be from 3-1,100%, but is more preferably 15%-300%. Thethickness of the films is preferably from 0.01 mm to 10 mm. The burststrength of the films, including the perforated films, is preferablyfrom 1-100 Kgf. The films may have short strength retention profiles,prolonged strength retention profiles, or combinations thereof. In oneembodiment, a short strength retention profile is 1 to 12 weeks, and aprolonged strength retention profile is 4 months to 5 years, morepreferably 4 months to 2 years. The films of the pouch may havedifferent degradation rates in vivo. Some films may degrade quicklywhile other films may degrade slowly. In another embodiment, the filmscomprise an additive or bioactive agent. The films can be produced byany suitable method, including melt extrusion, compression molding,injection molding, and solvent casting. In another embodiment, the filmsmay be laminated or thermoformed. In one embodiment, the films may belaminated and then the laminated article perforated and used to form apouch.

Pouches that can prevent rotation and migration of breast implants canbe prepared from the films described above. Such pouches can be producedfrom slow and fast degrading films, films of different molecularweights, films with different degrees of orientation, films of differentthicknesses, and films that are perforated, laminated or thermoformed,or combinations thereof.

F. Foams

The pouches may comprise foams. The foams are preferably made fromdegradable thermoplastic polymers, and even more preferably fromdegradable thermoplastic polyesters. The foams are preferably made fromthe degradable materials listed in Section II.A above. The foams can bemade by any suitable method, including melt foaming and solutionfoaming, including particulate leaching. In a preferred embodiment, thefoams are made from P4HB or copolymer thereof or poly(butylenesuccinate) or copolymer thereof. The foams may optionally becross-linked. Preferably the polymers of the foams have weight averagemolecular weights of 10 kDa to 1,200 kDa, but more preferably 50 kDa to600 kDa. The foams may have open cell or closed cell structures. In oneembodiment, the foams have an open cell content of at least 10%,preferably at least 25%, and more preferably at least 50%. The cellsizes may be up to 5 mm. The densities of the foams are preferably lessthan 1 g/cm³, more preferably less than 0.75 g/cm³, and even morepreferably less than 0.5 g/cm³. The thicknesses of the foams may be from0.01 mm to 10 mm. The foams may comprise additives or bioactive agents.The foams may have short strength retention profiles, prolonged strengthretention profiles, or combinations thereof. In one embodiment, a shortstrength retention profile is 1 to 12 weeks, and a prolonged strengthretention profile is 4 months to 5 years, more preferably 4 months to 2years. In another embodiment, the foams comprise an additive orbioactive agent.

Pouches that can prevent rotation and migration of breast implants canbe prepared from the foams described above. Such pouches can be producedfrom foams with open or closed cell structures, varying cell sizes anddensities, different molecular weights, and different strength retentionprofiles.

G. Textiles

The pouches may comprise textiles. The textiles are preferably made fromdegradable thermoplastic polymers, and even more preferably fromdegradable thermoplastic polyesters. The textiles are preferably madefrom the degradable materials listed in Section II.A above. In apreferred embodiment, the textiles are made from P4HB or copolymerthereof, or poly(butylene succinate) and copolymers thereof.

The thicknesses of the textiles may be from 0.01 mm to 10 mm. Thetextiles preferably have an average pore size diameter from 75 μm to 5mm, but more preferably from 500 μm to 5 mm, and even more preferablyfrom 800 μm to 5 mm. Preferably the polymers and fibers used to make thetextiles have weight average molecular weights of 10 kDa to 1,200 kDa,but more preferably 50 kDa to 600 kDa. The burst strength of thetextiles is preferably 0.1 Kgf to 100 Kgf, but more preferably 1 Kgf to50 Kgf. In embodiments, the textiles may have an elasticity of 15-75%,30-65%, 8-20%, or 5-25%, wherein the elasticity is measured as thepercent increase of an area of the textile when the area is subject todeformation in ASTM burst method D6797-02. The textiles may have shortstrength retention profiles, prolonged strength retention profiles, orcombinations thereof. In one embodiment, a short strength retentionprofile is 1 to 12 weeks, and a prolonged strength retention profile is4 months to 5 years, more preferably 4 months to 2 years. The pouch maybe formed from more than one textile, and the textiles used to form thepouch may degrade at different rates.

The pouches may be formed from woven and knitted textiles, or may beformed from non-woven textiles.

Woven and Knitted Textiles

In one embodiment, the textiles may be produced from monofilamentfibers, multifilament fiber, yarn, or combinations thereof. The textilesmay be produced from the fibers described in Section II.D above. Thefibers may be unoriented, partially oriented, highly oriented orcombinations thereof. The textiles may be knitted, woven, or braidedfrom the fibers. The textiles may also be made from the fibers bycrocheting. A particularly preferred textile for use in preparing thepouches is a warp knit mesh. In embodiments, the textiles with athickness of 0.5-10 mm, and more preferably 0.75-3 mm may be used tomake the front of a pouch. In another embodiment, textiles with athickness of 0.2-0.6 mm, and more preferably 0.2-0.4 mm, may be used tomake the back of the pouch. In another embodiment, textiles with anelasticity of 15-75% or 30-65% may be used to prepare the front of thepouch, and textiles with an elasticity of 5-25% or 8-20% may be used toprepare the back of the pouch, wherein the elasticity is measured as thepercent increase of the area when the area is subject to deformation inASTM burst method D6797-02 using a round ball.

In other embodiments, the textiles used to make the back, front bottom,and front top of the pouch have average pore diameter ranges of 0.5-3mm, 0.5-1 mm, and 0.1-1 mm, wherein the front bottom of the pouch is thearea placed in the lower pole nearest to the patient's skin, and thefront top of the pouch is the area placed in the upper pole nearest tothe patient's skin.

In a preferred embodiment, the textile is a mesh made from P4HBmonofilament fiber, or fiber comprising poly(butylene succinate) orcopolymer. In a more preferred embodiment, the P4HB monofilament mesh ormesh comprising poly(butylene succinate) or copolymer thereof, has aknitted or woven structure. A particularly preferred P4HB monofilamentmesh has substantially one or more of the following properties: anaverage pore diameter of 500 μm to 3 mm, a pore diameter ofapproximately 500-1,000 μm, thickness of 0.2-10 mm, 0.2-5 mm, or 0.4-0.8mm, areal density of 40-190 g/m² or approx. 140-190 g/m², suture pulloutstrength of 1-7 kgf, or 4-7 kgf, and a burst strength of 20-26 Kg or0.1-30 kgf/cm². A preferred mesh comprising poly(butylene succinate) orcopolymer thereof, has one or more of the following properties: (i) asuture pullout strength of at least 10 N, 1-7 kgf, or at least 20 N,(ii) a burst strength of 0.1 to 100 kgf, more preferably between 1 to 50kgf, or greater than 0.1 kPa, (iii) a thickness of 0.5-10 mm, morepreferably between 0.05-5 mm, (iv) an areal density of 5 to 800 g/m2,(v) a pore diameter of 5 μm to 5 mm, or more preferably 100 μm to 1 mm,or (vi) an average pore diameter of 0.1-3 mm. The textiles comprisingP4HB monofilament mesh or poly(butylene succinate) or copolymer thereofwith an elasticity of 15-75% or 30-65% may be used to prepare the frontof the pouch, and textiles comprising these polymers with an elasticityof 5-25% or 8-20% may be used to prepare the back of the pouch, whereinthe elasticity is measured as the percent increase of the area when thearea is subject to deformation in ASTM burst method D6797-02 using around ball. A more preferred mesh comprising poly(butylene succinate) orcopolymer thereof, has one or more of the following properties: (i) asuture pullout strength of 1 kgf to 20 kgf or 1-7 kgf, (ii) a burststrength of 1 to 50 kgf, more preferably 5 to 30 kgf, and even morepreferably 0.1-30 kgf/cm² (iii) a thickness of 0.2-0.6 mm, 0.5-10 mm, or0.1 to 1 mm, (iv) areal density of 40-190 g/m² or 100 to 300 g/m², and(v) pore diameter 100 μm to 1 mm. An even more preferred mesh comprisingpoly(butylene succinate) or copolymer thereof, has one or more of thefollowing properties: a pore diameter of 500±250 μm, thickness of0.4±0.3 mm, areal density of approx. 182±50 g/m², suture pulloutstrength of 5.6±2 kgf, and a burst strength of at least 3 kgf, and morepreferably at least 6 kgf. A preferred textile comprising poly(butylenesuccinate) or copolymer thereof is a monofilament knitted mesh.

Suitable P4HB monofilament meshes for preparing the pouches may beprepared according to the following procedure: P4HB Monofilament fibersfrom 49 spools, prepared as described in Section II. D, are mounted on acreel, aligned side by side and pulled under uniform tension to theupper surface of a “kiss” roller. The “kiss” roller is spun whilesemi-immersed in a bath filled with a 10% solution of TWEEN® 20lubricant. The TWEEN® 20 lubricant is deposited on the surface of thesheet of fiber. Following the application of TWEEN® 20, the sheet offiber is passed into a comb guide and then wound on a warp beam. A warpis a large wide cylinder onto which individual fibers are wound inparallel to provide a sheet of fibers. Next, warp beams are convertedinto a finished mesh fabric by means of interlocking knit loops. Eightwarp beams are mounted in parallel onto tricot machine let-offs and fedinto the knitting elements at a constant rate determined by the ‘runnerlength’. Each individual monofilament fiber from each beam is fedthrough a series of dynamic tension elements down into the knitting‘guides’. Each fiber is passed through a single guide, which is fixed toa guide bar. The guide bar directs the fibers around the needles formingthe mesh fabric structure. The mesh fabric is then pulled off theneedles by the take down rollers at a constant rate of speed determinedby the fabric ‘quality’. The mesh fabric is then taken up and wound ontoa roll ready for scoring. The P4HB monofilament mesh produced accordingto this method is scored ultrasonically with water, heat set in hotwater, and then washed with a 70% aqueous ethanol solution. A similarprocedure may be used to prepare a monofilament mesh of poly(butylenesuccinate) or copolymer thereof.

Non-Woven Textiles

In another embodiment, the textiles may be produced directly from thedegradable materials listed in Section II.A. In one preferredembodiment, the textiles have a non-woven structure. More preferably,the non-woven structure is dry-spun. Suitable methods to produce thetextiles directly from degradable materials, preferably thermoplasticpolymers and thermoplastic polyesters, include melt blowing,electrospinning, centrifugal spinning, spun bonding, and solventspinning, including dry spinning. Dry spinning is a particularlypreferred method for producing the textiles. The textiles may comprisean additive or bioactive agent. Dry spun textiles have a non-wovenstructure, as well as textiles produced by melt blowing,electrospinning, centrifugal spinning, spun bonding, and dry spinning.

In another preferred embodiment, the textile is a non-woven made fromP4HB, or poly(butylene succinate) or copolymer thereof, preferably bysolution spinning (also known as dry spinning). Suitable dry spun fibersof P4HB, or poly(butylene succinate) or copolymer thereof, may beproduced by dissolving P4HB or poly(butylene succinate) or copolymerthereof, in a solvent to form a polymer solution. Suitable solventsinclude chloroform, methylene chloride, acetone, and THF. A particularlysuitable polymer solution for P4HB is an 8% w/v solution of P4HB inchloroform. The polymer solution may be transferred to a solventreservoir connected to a nozzle that is aimed at a collector. Dry spunfibers are collected when the polymer solution is injected or pumpedinto a stream of accelerated gas exiting the nozzle. Suitable dry spunequipment has an inner and a concentric outer nozzle, which creates alow-pressure region near the orifice of the inner nozzle. A suitable gasis compressed air. The collector may be stationary, and the nozzle movedin order to form a non-woven at the collector. However, more preferably,the collector can be rotated and moved in all directions in order forthe collector to be completely covered by dry spun fiber, and ifdesired, to form a uniform coating of dry spun fibers on the collector.Generally, however, the distance between the collector and the nozzle isnot varied significantly. The collector is preferably in the shape of abreast implant such that a pouch comprising dry spun fibers can beformed on the collector. The non-woven pouch, so formed, will then be ofappropriate dimensions to encase a breast implant of the same dimensionsas the collector. In one embodiment, the dry spun fibers have averagediameters ranging from 0.01 μm to 50 μm. A particular advantage ofsolvent spinning P4HB fibers, and fibers of poly(butylene succinate) andcopolymers thereof, rather than melt spinning, is that the weightaverage molecular weight of the polymer does not decrease by more than10%, and even more preferably does not decrease by more than 5%, duringspinning.

Textile Compositions and Properties

Pouches that can prevent rotation and migration of breast implants canbe prepared from the woven, knitted and non-woven textiles describedabove. Such pouches can be produced from slow and fast degradingtextiles, woven and non-woven textiles, knitted textiles, warp knittedtextiles, degradable textiles of different molecular weights, textilesmade from unoriented, partially oriented and fully oriented fibers,textiles made from monofilament fiber, multifilament fiber, yarn, andcombinations thereof, textiles made directly from degradable materials,including by electrospinning, melt-blowing, solvent spinning includingdry spinning, centrifugal spinning and spun-bonding, and textiles withdifferent burst strengths, or combinations of the above.

In one embodiment, the pouch comprises an auxetic structure, andpreferably an auxetic mesh.

In one embodiment, the textile may comprise a bioactive agent. Thebioactive agent may be coated on the textile, the bioactive agent may becontained within the textile, or a combination thereof. In a preferredembodiment, the bioactive agent may be applied to the textile byspraying the textile with a solution of the bioactive agent or dipcoating the textile in a solution of the bioactive agent. In anotherpreferred embodiment, the textile comprising the bioactive agent may beformed directly in one step. For example, a solution of polymer andbioactive agent may be solution spun, dry spun or electrospun to form atextile comprising the bioactive agent. In a particularly preferredembodiment, the pouch may be formed from a P4HB textile, or textile ofpoly(butylene succinate) or copolymer thereof, coated with one or morebioactive agents, or by forming the P4HB textile, or textile ofpoly(butylene succinate) or copolymer thereof, comprising the one ormore bioactive agents in one step, for example, by melt or solutionprocessing, dry spinning, solvent spinning, centrifugal spinning,spun-bonding, melt-blowing, melt spinning or electrospinning. In apreferred embodiment, the textile used to form the pouch is a P4HBtextile, or textile of poly(butylene succinate) or copolymer thereof,comprising one or more antibiotics.

III. Methods of Manufacturing Pouches to Limit Movement of BreastImplants

A variety of methods can be used to manufacture the pouches, and severaldifferent examples of pouches to limit rotation and migration of breastimplants are described herein. The pouches limit the rotation of breastimplants after implantation in the patient. In embodiments, pouchesprevent breast implants from rotating more than 45 degrees, and morepreferably more than 30 degrees, after implantation. In otherembodiments, the pouches limit migration of breast implants after thebreast implant is placed in the pouch, and the pouch is implanted in thepatient. Limiting migration means that the pouch can be used to preventthe breast implant from migrating a threshold distance afterimplantation. In embodiments, the threshold distance is 5 cm, and morepreferably 3 cm or 1 cm. Prevention of migration is important to preventpocket stretch, ptosis, and lateral displacement of breast implants.

The pouches may have three-dimensional shapes. Preferably, the pouch hasthe same shape, identical shape, or a similar shape, as the breastimplant that is placed inside the pouch. The pouches are preferably justslightly larger than the breast implant in order to allow insertion ofthe breast implant into the pouch.

In other embodiments, the pouches have an elasticity that allows a tightfit to be formed between the pouch and the breast implant. Preferably,the volume of the pouch is no more than 20% larger than the breastimplant that will be placed inside the pouch, more preferably no morethan 10% larger than the breast implant that will be placed inside thepouch, and even more preferably no more than 5% larger than the breastimplant that will be placed inside the implant. Preferably, the volumeof the pouch is between 150-800 cc, and more preferably between 165-800cc. Preferably the width of the base of the pouch is 7.4-17.2 cm, andmore preferably 9-16.5 cm, and has a projection ranging between 4 and8.5 cm, and more preferably 4.2-7 cm.

The pouch may have a dome shape, round shape or anatomical shape. Thepouch may comprise surfaces with flat, round, curved or anatomicalshapes. The shape of the pouch preferably follows the contours of thebreast implant that will be inserted in the pouch. The breast implantsmay include silicone and saline breast implants, anatomic and roundbreast implants, and surface textured and non-textured breast implants.Non-limiting examples of breast implants include: (i) Mentor'sMemoryShape® breast implants, MemoryGel® breast implants, and Spectrum®breast implants; (ii) Allergan's Natrelle® breast implants, includingtheir gummy breast implants, Inspira® responsive, soft touch andcohesive breast implants, Natrelle® 410 anatomical implants, Natrelle®saline-filled breast implants, and Biocell™ breast implants; (iii)Sientra's Opus™ breast implants, including their smooth round, texturedround and textured shaped, high strength cohesive breast implants, HSCand HSC+; (iv) Anion Laboratories' Monobloc® silicone and hydrogel-CMCbreast implants; (v) Cereplas Cereform® breast implants; (vi)Establishment Labs' Motiva® breast implants, including their Ergonomix™and Round breast implants; (vii) GC Aesthetics' Eurosilicone® and Nagor®breast implants, including Impleo™, CoGEL™, Round Collection byEurosilicone®, The Matrix by Eurosilicone®, GFX™ by Nagor®, and RGI™ byNagor® breast implants; (viii) Groupe Sebbin's inflatable, cohesiveround, high cohesive round, short anatomical and tall anatomical breastimplants; (ix) Guangzhou Wanhe Plastic Materials' Snow.Lambe,Crystal.Lambe, and Lambe breast implants; (x) Hans Biomed's BellaGelbreast implants; (xi) Ideal Implant Incorporated's Ideal Implant® breastimplants; (xii) Polytech Health and Aesthetics' Mesmo®, Polytxt®,Microthane®, SublimeLine® and Diagon\Gel® 4 Two breast implants; and(xiii) Silimed breast implants including conical, round and anatomicalshapes. Additional examples of breast implants for use with embodimentsof the subject invention are disclosed by Maxwell and Gabriel, Theevolution of breast implants, Plast. Reconstr. Surg. 134:12S, 2014, andreferences therein, U.S. Pat. No. 10,052,192 to Schuessler, U.S. Pat.No. 6,074,421 to Murphy, U.S. Pat. No. 5,007,929 to Quaid, U.S. Pat. No.8,211,173 to Keller, U.S. Pat. No. 4,960,425 to Yan, U.S. Pat. No.4,380,569 to Shaw, U.S. Pat. No. 5,902,335 to Snyder, U.S. Pat. No.3,293,663 to Cronin, U.S. Pat. No. 4,863,470 to Carter, U.S. Pat. No.4,773,909 to Chaglassian, U.S. Pat. No. 6,074,421 to Murphy, U.S. Pat.No. 8,377,127 to Schuessler, and U.S. Pat. No. 8,043,373 to Schuessler.

In embodiments, the shape of the pouch preferably drapes the insertedbreast implant. The size and shape of the pouch used in a procedure maybe based upon the surgeon's and patient's choice of the breast implantsize and shape, and the need to match those requirements closely to thepouch size so that the implant cannot rotate when inserted in, andsecured in, the pouch. In an embodiment, the pouch has elasticity thatmakes it possible to easily insert the breast implant into the pouchwith a tight fit. Preferably, the pouch is formed with a front area ofthe pouch having an elasticity of 15-75% or 30-65%, and the back area ofthe implant having an elasticity of 5-25% or 8-20%, wherein theelasticity is measured as the percent increase of the area when the areais subject to deformation in ASTM burst method D6797-02 using a roundball. In this embodiment, the front area of the pouch is the area placedjust beneath the patient's skin, and the back area of the pouch is thearea placed on the chest wall.

Preferably the pouches are porous, or become porous after implantation,and even more preferably the pouches are macro-porous or becomemacro-porous after implantation. In a preferred embodiment, the pouchescomprise pores with average pore diameters of at least 100 μm, morepreferably at least 250 μm, and even more preferably at least 500 μm. Aparticularly preferred pore diameter is 800 μm±300 μm. A particularlypreferred pore size is 0.64 mm²±0.3 mm². The pouches may be preparedfrom porous materials, or they may be prepared from non-porousmaterials. In embodiments, pouches prepared from non-porous materialsare then perforated.

In one embodiment, a pouch for fixation of a breast implant may beprepared with different pore sizes in different areas of the pouch.Preferably, the pouch is prepared with larger pores around the perimeterof the pouch and on the back of the implant (which contacts the chestwall after implantation), and smaller pores on the top front side of thepouch (which is placed in the upper pole of the breast under the skin ofthe patient). The larger pores on the back of the pouch improve thedrapeability of the pouch. The smaller pores on the top front of thepouch increase the surface area available for coating with fat, andallow delivery of more fat to the upper pole of the breast. In apreferred embodiment, the average pore sizes of the pouch are: 0.5-3 mmon the back of the pouch, 0.1-1 mm on the top front of the pouch, and0.5-1 mm on the bottom front of the pouch (which is placed in the lowerpole of the breast under the skin of the patient).

In a preferred embodiment, the front of the pouch (that is placedbeneath the patient's skin) has a thickness of 0.5-10 mm, and the backof the pouch (that is placed next to the chest wall) has a thickness of0.2-0.6 mm, and more preferably from 0.2-0.4 mm. Pouches with thickerfront areas make it possible to avoid the formation of ripples andindentations on the patient's skin caused by ripples present on breastimplants, and reduce or eliminate the palpability of the breast implant.Use of pouches with thicker front areas is particularly important inpatients where the skin is thin, or in patients where excessive amountsof tissue have been removed such as in radical mastectomy procedures.

The pouches are preferably made from resorbable polymers, morepreferably from resorbable fibers, and even more preferably fromresorbable fibers that degrade in less than 5 years, more preferably inless than 2 years, and even more preferably in less than 1 year. Thepouches may comprise fibers with fast and slow rates of degradation.

In another embodiment, the pouches are formed by 3D-printing. Suitablemethods for 3D-printing the pouches include fused filament fabrication,fused pellet deposition, melt extrusion deposition, selective lasermelting, printing of slurries and solutions using a coagulation bath,and printing using a binding solution and granules of powder.Preferably, the pouches are 3D-printed using P4HB or poly(butylenesuccinate) or copolymer thereof.

In a preferred embodiment, there is an opening in the pouch to allowinsertion of the breast implant. The opening may be made after the pouchhas been constructed, or during construction of the pouch. The openingmay be made in a component of the pouch, such as the base or rear of thepouch, prior to assembly of the pouch. The opening can be a slit in thepouch, preferably in the base of the pouch or on the side of the pouch.The slit can be reinforced. The slit can be elasticated. The slit can belinear, or curve shaped. In an embodiment, the pouch can comprise acover or seal placed over the opening where the breast implant isinserted.

In a preferred embodiment, the slit will contact the chest wall when thepouch is implanted. In such an embodiment, the slit is placed in theback or rear of the pouch, that is placed on the chest wall as shown,for example, in FIGS. 19A-19C. This orientation of the slit is preferredsince it prevents the breast implant from being released from the pouchin situ. Even more preferably, the pouch comprises a slit in the back ofthe pouch and incorporates tabs to allow fixation to the chest wall suchthat the slit of the pouch will be on the chest wall when implanted.

The manufactured pouches preferably have an endotoxin content of lessthan 20 endotoxin units making them suitable for implantation in apatient.

The pouches may comprise the additives listed in Section II.B and thebioactive agents listed in Section II.C.

Pouches Limiting Breast Implant Rotation by a Cinching Mechanism

In one preferred embodiment, the pouches are designed to limit rotationof breast implants using a cinching mechanism. A diagram of a pouch 10with a cinching mechanism 12 is shown in FIG. 1 . The pouch 10 comprisesa slit 14 for insertion of a breast implant, and a draw cord 12 runningaround the perimeter of the pouch that can be tightened to limitrotation of a breast implant inside the pouch. In an embodiment, poucheswith a cinch mechanism can be prepared by molding processes. In theseprocesses, fiber-based structures, films, foams, 3D-printed structures,and combinations thereof, are molded into shapes to accommodate breastimplants. Fiber-based structures include structures formed bymelt-blowing, solution spinning, dry spinning, electrospinning,centrifugal spinning, melt spinning, knitting, weaving, braiding,entangling of fibers, 3D-printing, as well as embedded fibers in otherstructures such as foams, films, laminates, and fibers coated with filmsand foams. Fiber-based structures may comprise monofilament fibers,multifilament fibers, hollow fibers, and yarns. Fiber-based structuresinclude non-woven structures, knitted structures, braided structures,textiles, fabrics, and woven structures. Preferred fiber-basedstructures are (i) knitted monofilament meshes, and even more preferablya knitted monofilament mesh comprising P4HB or copolymer thereof, orpoly(butylene succinate) or copolymer thereof, and (ii) dry spunnonwovens, and even more preferably P4HB dry spun nonwovens or dry spunnonwovens of poly(butylene succinate) or copolymer thereof.

In a preferred embodiment, the pouches with cinch mechanism (as shown inFIG. 1 ) are prepared by thermoforming fiber-based structures, foams,films, or laminates. In a particularly preferred method, the pouches areformed using a mold substantially in the shape, or part of the shape, ofa breast implant. The mold may, for example, be dome shaped, round,spherical, semi-spherical, or an anatomical shape. Preferably the moldis the same size or slightly larger than the breast implant, butpreferably the volume of the mold is not more than 20% larger, morepreferably not more than 10% larger, and even more preferably not morethan 5% larger than the breast implant. In one embodiment, the mold ismade from metal.

With reference to FIGS. 2A-2B, in a preferred embodiment, the method ofmaking the pouch for a breast implant with a cinch mechanism comprisesthe steps of forming a front half 20 of a pouch and a back or rear half30 of a pouch, and joining the front half and back half together. Inthis embodiment, the front half 20 of the pouch refers to the part ofthe pouch that will be placed in the anterior position in the patient,and the back half 30 of the pouch refers to the part of the pouch thatwill be placed in the posterior position in the patient. The back half30 of the pouch may also be referred to as the rear of the pouch.

The front half 20 of the pouch encompasses most, and preferably all, ofthe projection of the breast implant from the chest of the patient. Thefront and back halves of the pouch may be joined by any suitable method,including sewing and welding. For example, the halves may be joinedusing an ultrasonic spot welder or using a knitting machine.

In one embodiment, the front half of the pouch with a cinch mechanism ismade by thermoforming. Preferably, a fiber-based structure isthermoformed to make the front half of the pouch. The fiber-basedstructure is preferably porous. The front half of the pouch may also bethermoformed from a non-fiber based structure, such as a film, laminate,or foam, or structure comprising a combination of fibers, films, orfoams. The front half of the pouch may also be thermoformed from anon-porous structure, and later perforated. In a preferred embodiment,the front half of the pouch is made by thermoforming a knitted mesh,more preferably a knitted monofilament mesh, and even more preferably aknitted monofilament mesh comprising P4HB or copolymer thereof, orcomprising poly(butylene succinate) or copolymer thereof. In aparticularly preferred embodiment, the pouch is formed by joining afront half of a pouch made by thermoforming P4HB knitted monofilamentmesh, to a back half of a pouch made from P4HB knitted mesh, or byjoining a front half of a pouch made by thermoforming a monofilamentmesh of poly(butylene succinate) or copolymer thereof to a back half ofa pouch made from a mesh of poly(butylene succinate) or copolymerthereof. The P4HB and poly(butylene succinate) or copolymer thereofmonofilament fibers of the mesh used to prepare the front and backhalves are preferably oriented, that is, the P4HB and poly(butylenesuccinate) or copolymer thereof monofilament fibers have been stretchedduring their manufacture.

The front half of the pouch with a cinch mechanism may be thermoformedfrom a P4HB monofilament knitted mesh, prepared as described in SectionII.G above, by placing the mesh over a suitable metal mold, such as ahalf-dome mold, and heating the mesh under tension. Suitable conditionsfor heating the P4HB mesh are 57° C. for 5 min. After heating to shapethe mesh, the shaped mesh can be quenched, for example, in a cold-waterbath. Suitable conditions for quenching are immersion in a cold-waterbath set at 9° C. for 10 min. After quenching, the shaped front half ofthe pouch can be removed from the mold, and attached to a suitably sizedback half to form the pouch.

The front half or back half of the pouch with a cinch mechanism, or bothhalves, may comprise an opening to allow insertion of the breast implantinto the pouch. The opening may be inserted before or after theconstruction of the pouch. In one preferred embodiment, the opening isplaced in the back half of the pouch. The opening is preferably made inthe back half of the pouch prior to attaching it to the front half ofthe pouch. In another preferred embodiment, the opening is made afterassembly of the pouch from the front and back halves. The latter openingmay in one embodiment be a V-shaped opening prepared by the removal of awedge shape from the pouch. An opening may be made in a pouch comprisingP4HB knitted monofilament mesh, or monofilament mesh of poly(butylenesuccinate) or copolymer thereof, using a laser, or by another suitablecutting method.

The thermoformed pouches with cinch mechanisms may comprise suturestraps so that the pouches can be anchored in place in the patient.Preferably the straps are placed around the perimeter of the pouch. Anynumber of straps may be incorporated, including 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, and 12, but more preferably 4 straps can be incorporated onthe perimeter of the pouch spaced at 90 degrees from each other. In oneembodiment, a pouch with straps may be prepared by forming a circularmesh, as described above, with straps placed around its perimeter, andjoining it to a thermoformed mesh front half, also prepared as describedabove. Preferably the straps are made from P4HB monofilament mesh ormesh made from poly(butylene succinate) or copolymer thereof.

Various methods may be used to secure the breast implants inside thepouches. In one preferred embodiment, the pouch with the cinch mechanismcomprises a draw cord that can be tightened to prevent rotation of thebreast implant inside the pouch. Tightening the draw cord causes thepouch to cinch or slightly compress the breast implant, and limitsrotation of the breast implant inside the pouch. In one embodiment, thedraw cord is placed around the perimeter of the pouch, preferably, in analternating pattern through slots in the perimeter of the pouch.

A pouch 10 with a draw cord 12 (see, e.g., FIG. 1 ) can be preparedusing, for example, the following method steps: (i) a mesh is cut toform two circular shapes, a front half 20 and a back half 30, (ii) thefront half 20 is further cut to insert a series of holes 22 around theperimeter for later insertion of a draw cord, and then thermoformed toform a semi-spherical 3D shape suitable for later insertion of a breastimplant, (iii) the back half 30 shape is then attached to the front halfshape to form the pouch, (iv) a slit 14 is inserted in the side of thepouch to allow insertion of a breast implant into the pouch, and (v) adraw cord 12 is laced around the perimeter of the pouch alternatingthrough the holes 22 cut in step (ii) as illustrated in FIG. 1 .Preferably, the mesh used in this method is a monofilament mesh, morepreferably a warp knit monofilament mesh, and even more preferably awarp knit monofilament mesh comprising P4HB or copolymer thereof, orcomprising poly(butylene succinate) or copolymer thereof. A P4HBmonofilament knitted mesh may be thermoformed by molding the mesh in ahot water bath over a metal mold with the mesh under tension, and thenquenching the mesh in a cold-water bath. The two halves of the mesh, thefront and back halves, are preferably sewn or welded together to formthe pouch in step (iii) above. Different sizes and shapes of pouches maybe prepared by using molds of different sizes, including round shapesand anatomical shapes. The draw cord may, for example, be amonofilament, multifilament, braid, or tape. Suture straps for anchoringthe pouch in the patient may also be incorporated into the pouch bycutting the mesh for the back half of the pouch in step (i) so thatstraps of mesh protrude from the perimeter of the circular mesh. Anynumber of suture straps can be included, including 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, but more preferably four straps are included aroundthe perimeter of the circular mesh at 90 degree intervals.

Pouches with Slots that Mate with Tabs of Tabbed Breast Implants toLimit Rotation of the Breast Implant

In another preferred embodiment, a pouch 110 is designed for use with atabbed breast implant, and mate with the tabs 122 of the breast implantsto limit rotation of the breast implants. A diagram of a slotted pouchcontaining a tabbed breast implant is shown in FIGS. 4A, 4B with thetabs 122 of the breast implant protruding from the inside of the pouch110, through the pouch slots, to the outside.

A cross-section of the slotted pouch 110 containing a tabbed breastimplant 120 is shown in FIG. 6 . A preferred method of making a pouchwith slots that mate with tabs of a tabbed breast implant to limitrotation of the breast implant comprises the steps of: (i) solutionspinning a nonwoven on a collector to form a pouch, (ii) cutting thenonwoven in order to remove it from the collector, and (iii) creatingmating slots in the nonwoven pouch to receive tabs from a tabbed breastimplant.

With reference to FIG. 5 , a suitable equipment set up 200 for solutionspinning a pouch that can be used with a tabbed breast implant comprisesa collector 210, a spray nozzle 220, a compressed gas line, a reservoirfor a spinning solution 224, and a motor 230 that can either move thenozzle around the collector, or vice versa, in order to spray all thecollector with fibers and preferably produce an even coating of fibers234 on the collector. The collector 210 is preferably in the shape ofthe breast implant that will be inserted inside the pouch, and can, forexample, be made from aluminum or stainless steel. The collector may,for example, be round, a sphere, a semi-sphere, or an anatomical shape.The volume of the collector is preferably 80-800 cm³. The width of thecollector is preferably 7.4-17.2 cm. A suitable nozzle for dry spinninghas an inner and a concentric outer nozzle, which creates a low-pressureregion near the orifice of the inner nozzle. Suitable spinning solutionscan be prepared by dissolving polymers in volatile organic solvents.Suitable organic solvents include chloroform, methylene chloride,acetone, and THF. The concentration of the polymer in the solvent willvary depending upon the solubility of the polymer, and its solutionviscosity. Preferred concentrations of the polymer in the solventinclude 3-10% w/v. Dry spun fibers are deposited at the collector bypumping a polymer solution through the nozzle, and injecting it into astream 242 of accelerated gas directed at the collector. The rate ofinjection of the polymer solution is preferably controlled by a pumpdrive. Suitable pump speeds will depend upon the particular polymersolution, and the equipment set up. Suitable sources of accelerated gasare compressed air, nitrogen and helium. Suitable pressures of thecompressed gas include 5-3,500 kPa. In an embodiment, the compressed gasmay be heated. In a preferred embodiment, the collector is kept at afixed distance from the nozzle, but rotated (R) and moved axially (A) sothat an even coating of dry spun fibers is deposited on the collector. Apreferred distance (D) of the collector from the nozzle is 40-80 cm. Inan embodiment, the collector may be rotated at 10-100 rpm, and morepreferably 25-60 rpm. The average diameter of the dry spun fibersdeposited at the collector is preferably 0.01-50 μm, and more preferably5-30 μm. The preferred thickness of the fibers deposited on thecollector should be sufficient to ensure the integrity of the pouch. Inone embodiment, the thickness of the fibers deposited at the collectoris 0.25-3 mm, and more preferably 0.5-1 mm. After collection of the dryspun fibers at the collector, the non-woven may be removed from thecollector by cutting a slit in the non-woven. Preferably, a V-shapedslit is cut in the non-woven to allow removal of the non-woven pouchfrom the collector. The slit is preferably made in the non-woven pouchin a position where the same slit can be used to insert a breast implantinside the non-woven pouch. Slits may be cut in the non-woven using asharp blade. Once the pouch has been removed from the collector, slotsthat will mate with tabs on a tabbed breast implant are cut in thepouch, preferably with a sharp blade. Preferably, the slots are locatedaround the perimeter of the pouch. FIGS. 4A, 4B depict four slots cut inthe perimeter of a pouch, and a tabbed breast implant inserted insidethe pouch so that its tabs protrude through the slots. The number ofslots cut in the pouch and their locations will preferably match thenumber and locations of the tabs on the tabbed breast implant. In onepreferred embodiment, there are 1-6 tabs on the tabbed breast implant,and 1-6 mating slots on the pouch, and more preferably 4 tabs on thetabbed breast implant and 4 mating slots on the pouch as shown in FIGS.4A, 4B.

A particularly preferred polymer for preparing a non-woven pouch is P4HBor copolymer thereof. Another particularly preferred polymer forpreparing a non-woven pouch is poly(butylene succinate) or copolymerthereof. P4HB and poly(butylene succinate) or copolymer thereof may bedry spun without any significant loss of weight average molecularweight. In a preferred embodiment, the P4HB and poly(butylene succinate)or copolymer thereof do not lose more than 10% of their weight averagemolecular weights during dry spinning of a non-woven pouch.

Pouches Limiting Breast Implant Movement Prepared by Warp Knitting usinga Knitting Machine with a Double Needle Bed

With reference to FIGS. 8, 9 , in yet another preferred embodiment, apouch for limiting the movement of a breast implant may be prepared bywarp knitting using a knitting machine with a double needle bed. Anexample of a pouch 400 prepared using a knitting machine with a doubleneedle bed is shown in FIG. 9 . The pouch 400 may be formed by knittinga tubular construct 402, for example, with the loops shown in FIG. 8 ,but wherein sections of the tube are knitted together at the edges 404and in the connected areas 410, 412 shown in FIG. 8 and the “knittedclosure” region 430 shown in FIG, 9.

In one embodiment, a knitting machine is set up so that mesh is knitseparately on the front and back beds of the knitting machine, exceptfor the edges where fiber is knit simultaneously on the front and backbeds to form a tubular structure. It is to be appreciated the enclosureis shown having an initial 2D or flattened sleeve construct. After thebreast implant is placed within the enclosure, the enclosure takes asecond 3D construct more closely in the shape of the breast implantitself. The pouch is preferably knit with closed loop stitches knitseparately on the front and back beds. In embodiment, the upper andlower connected areas 410, 412 shown in FIG. 8 are also knitsimultaneously on the front and back beds of the knitting machine. Theconnected areas 410, 412 or seams preferably comprise concave and convexshapes as shown in FIG. 8 . In this manner, a pouch is formed in thetubular knit in the area located inside the connected area.

In embodiments, the connected areas or seams join two separate sheetstogether and form the perimeter of the cavity to hold the breastimplant.

In embodiments, a single sheet is folded to form two sides of the pouch,and the connected areas or seams join the sides together and form theperimeter of the cavity to hold the breast implant.

After knitting, the tubular knit may be cut and trimmed to shape thepouch. Although the figures illustrate a particular shape of pouch andenclosure, the invention is not so limited except where specificallyrecited in the appended claims. The shape of the pouch may vary widelyprovided it can limit movement of the breast implant once implanted.

In a preferred embodiment, the pouch further comprises regions or areas440 outside of the connected areas as shown in FIG. 9 . These connectedareas 430 can be used by the surgeon to fixate the pouch to tissueduring implantation. Preferably, extension areas 440 are sutured orstapled to the patient's tissue.

With reference again to FIG. 9 , a slit 450 may be cut on one side ofthe knitted pouch to create an opening for insertion of a breast implantinto the pouch. The slit should be sufficiently wide to allow insertionof the breast implant. Preferably the slit is located in the rear (orback) of the pouch so as to be placed against the chest wall of thepatient once implanted.

The pouch 400 is preferably knit with monofilament fiber. Preferably,the monofilament fiber has a diameter from 0.04 mm to 0.35 mm, but morepreferably 0.05 to 0.2 mm. In a particularly preferred embodiment, thepouch is knit with monofilament fiber comprising P4HB or poly(butylenesuccinate) or copolymer thereof.

In an alternative embodiment, a warp knitted pouch may be prepared asdescribed above using a double needle bed, but without knitting of theconnected areas shown in FIG. 8 . Instead of knitting the connectedareas, the pouch may be formed by knitting a hollow tube, and using anultrasonic welder to form heat seals in the connected areas shown inFIG. 8 . A pouch is thus formed from a tubular knitted mesh by weldingtogether the front and back meshes of the tubular knit, followed bytrimming. Preferably, the tubular mesh is welded so the connected areascomprise concave and convex shapes as shown in FIG. 8 , but there is noparticular limitation on the shape of the pouch provided it can limitmovement of the breast implant once implanted in a patient.

As described above, a slit may be introduced in the pouch to allow theintroduction of the breast implant into the pouch. The pouch ispreferably knit with monofilament fiber. Preferably, the monofilamentfiber has a diameter from 0.04 mm to 0.35 mm, but more preferably 0.05to 0.2 mm. In a particularly preferred embodiment, the pouch is knitwith monofilament fiber comprising P4HB or poly(butylene succinate) orcopolymer thereof.

In yet another embodiment, and with reference to FIG. 10 , a pouch 500for limiting movement of a breast implant 502 has a semi-circular shape.In a sense, the pouch has a pita pocket-like shape.

It may be prepared from a tubular knit, produced for example asdescribed above, and include a concave-shaped lower end 510 and a slit520 or opening at the upper end of the pouch instead of being located onthe front or rear sides of the pouch as shown in FIG. 9 . The pouchshown in FIG. 10 also lacks the convex-shaped upper end.

Although a concave-shaped lower end is illustrated and preferred in someembodiments, the shape of the lower end of the pouch may vary widely.

The pouch is preferably knit with monofilament fiber. Preferably, themonofilament fiber has a diameter from 0.04 mm to 0.35 mm, but morepreferably 0.05 to 0.2 mm. In a particularly preferred embodiment, thepouch is knit with monofilament fiber comprising P4HB or poly(butylenesuccinate) or copolymer thereof.

The pita pocket-shaped pouch shown in FIG. 10 may also be prepared froma tubular knit prepared as described herein, except with a lower portionthat is formed by ultrasonic welding instead of knitting. Knitting ishowever preferred since it allows uniform stretching of the pouch.

Breast Implant Fixation Device Comprising a Pouch with Different PoreSizes, Different Elasticities, and or Different Thicknesses of Front andBack Regions

In a further embodiment, a breast implant fixation pouch device may beprepared from two or more materials with different pore sizes, two ormore materials with different elasticities, or two or more materialswith different thicknesses, or a combination thereof. In one embodiment,suitably shaped materials with different pore sizes, differentthicknesses or both different pore sizes and different thicknesses maybe joined together, for example, by sewing, gluing, or welding, in orderto form a pouch for an implant. For example, two semicircular pieces810, 820 of material may be sewn to a round piece 830 of material toform a pouch 800 for an implant as shown in FIGS. 15-17B. The pieces ofmaterial may be stitched together along the stitch lines 840 shown inFIG. 15 . Alternatively, two round but different pieces of material maybe stitched together, and then a cut made in one of the pieces ofmaterial to create an opening 850 in the pouch for insertion of a breastimplant. The materials used to construct the pouch are preferablyporous, and more preferably are textiles, including woven, non-woven,monofilament, multifilament, and knitted textiles. In a particularlypreferred embodiment, the textiles are monofilament meshes, and evenmore preferably monofilament meshes with a Marlex knit pattern. Thematerials forming the pouch are preferably chosen so that the front ofthe pouch (which is placed just under the patient's skin) has athickness of 0.5-10 mm, and the back of the pouch (which is placed onthe chest wall of the patient) has a thickness of 0.2-0.6 mm, and morepreferably from 0.2-0.4 mm. In another embodiment, the materials may bechosen so that the front of the pouch (which is placed just under thepatient's skin) has an elasticity of 15-75% or 30-65%, and the back ofthe pouch (which is placed on the chest wall of the patient) has anelasticity of 5-25% or 8-20%, wherein the elasticity is measured as thepercent increase of an area of the material when the area is subject todeformation in ASTM burst method D6797-02 using a round ball. In aparticularly preferred embodiment, the materials may be chosen so thatthe front of the pouch has an elasticity of 30-65%, and the back of thepouch has an elasticity of 8-20%. In a further embodiment, the averagepore diameters of the materials forming the pouch are selected from oneor more of the following: 0.5-3 mm in the back of the pouch (which isplaced on the chest wall of the patient), 0.5-1 mm in the front bottomof the pouch (where the pouch material is placed in the lower pole justunder the skin of the patient), and 0.1-1 mm in the top front of thepouch (where the pouch material is placed in the upper pole just underthe skin of the patient). In another embodiment, the materials used toform the pouch have one or more of the following properties: (i) burststrength of 0.1 to 30 kgf/cm²; (ii) suture pullout strength of 1-7 kgf,and (iii) areal density of 40 to 190 g/m2. In a particularly preferredembodiment, the pouch materials comprise poly-4-hydroxybutyrate orcopolymer thereof or poly(butylene succinate) or copolymer thereof, evenmore preferably in the form of textiles or other porous constructs. Inanother embodiment, the breast implant fixation pouch device is coatedwith one or more of the following: a bioactive agent, antibiotic,antimicrobial, autologous fat, fat lipoaspirate, injectable fat, adiposecells, fibroblast cells, stem cells, collagen, and hyaluronic acid.

Examples of different methods to produce suitable breast implantfixation pouches with different pore sizes, different elasticities, anddifferent thicknesses of the pouch's front and back areas are describedin Examples 9-11.

IV. Methods of Implanting Pouch containing Breast Implant to LimitMovement

The pouches containing the breast implants may be implanted in the body.Preferably, the assembly of the pouch containing the breast implant isimplanted in the breast. More preferably, the pouch is implanted in abreast where the patient is seeking reconstruction or augmentation ofthe breast.

The breast implants are preferably placed in the pouches prior toimplantation, however, the pouch may be implanted in the patient, andthen the breast implant placed in the pouch. The method of securing thebreast implant inside the pouch will depend upon the particular designof the pouch, and also on the breast implant. For example, in the caseof the pouch of FIG. 1 , the breast implant is secured inside the pouchby tightening the draw cord. Tightening the draw cord cinches the breastimplant applying pressure to the implant, and limiting movement of thebreast implant inside the pouch.

The pouch shown in FIGS. 4 and 6 is designed for use with tabbed breastimplants that comprise one or more tabs, interlocks, or protuberances.These breast implants may be inserted into the pouch through slits inthe pouch, preferably in the base of the pouch (the area of the pouchthat will be in contact with the patient's chest wall). The breastimplant is then oriented inside the pouch so that the tabs orprotuberances on the breast implant fit through, or mate with, the slotson the pouch, as shown in FIGS. 4 and 6 . Once the tabs or protuberanceson the breast implant engage with the pouch, rotation and movement ofthe breast implant inside the pouch is limited.

In a preferred embodiment, the pouch containing the breast implant isused in breast reconstruction, particularly following mastectomy, andbreast augmentation, including augmentation mastopexy. The pouchcontaining the breast implant may be placed in a pocket formed in thebreast solely from the patient's tissues, or in a pocket that is formedusing an implant, for example, a pectoralis extender, such as anacellular dermal matrix (ADM), P4HB mesh, mesh of poly(butylenesuccinate) or copolymer thereof, or other material that can form ahammock or sling in the breast. If desired the pocket may be formed orenlarged using a tissue expander.

In an embodiment, a procedure for implanting the pouch containing thebreast implant following mastectomy comprises forming a pocket in thebreast of a patient suitable for receiving the pouch containing thebreast implant, and implanting the pouch containing the breast implant.In a preferred procedure for implanting the pouch containing the breastimplant in a patient after mastectomy, the method of implantationcomprises: (i) implanting a tissue expander in the patient; (ii)implanting a pectoralis extender in the vicinity of the tissue expander;(iii) expanding the tissue expander; (iv) removing the tissue expander;and (v) implanting the pouch containing the breast implant in the pocketcreated in the breast of the patient. Preferably, the pectoralisextender is sutured to the detached pectoralis major muscle, which hasbeen mobilized in preparation for placement of a tissue expander. Thesuture may be either permanent or absorbable, but is preferablyabsorbable. Once sutured to the pectoralis major muscle, the pectoralisextender can be used as a sling or hammock to cover the inferolateralportion of an inserted tissue expander. The tissue expander may bepartially inflated or uninflated prior to implantation. In the lattercase, the tissue expander may be partially inflated immediately afterimplantation.

In an embodiment, a procedure for implanting the pouch containing thebreast implant in patients desiring breast augmentation comprisesimplanting the pouch in the pre-pectoral position (subglandularposition) to eliminate the need to detach the muscle from the chestwall, and to reduce pain associated with detachment of the muscle fromthe chest wall. However, in other embodiments, the pouch containing thebreast implant may, if desired, be implanted in the sub-pectoralposition or sub-muscular position.

Optionally, the pouch containing the breast implant may be fixated inplace. In an embodiment, the pouch comprises suture straps, or similarextensions, that may be fastened to the patient's tissue. The straps maybe fastened to the patient's tissue using sutures, tacks, clips,staples, or similar fastening devices. Alternatively, the pouch may befixated in place by directly attaching the pouch to the chest wall ofthe patient, for example, using sutures, tacks, staples or otherfastening devices and materials.

EXAMPLES

The present invention will be further understood by reference to thefollowing non-limiting examples.

Example 1: Pouch with Draw Cord Cinch Mechanism to Limit Rotation andMovement of Breast Implant

A pouch to limit rotation and movement of a breast implant with thedesign shown in FIG. 1 was prepared from a P4HB monofilament mesh. Themesh was knit on a 14-gauge warp knitting machine from USP size 5-0 P4HBmonofilament fiber as described in Section II.G. The P4HB monofilamentfiber had an elongation to break of 55%, and a weight average molecularweight of 340 kDa. After knitting, the mesh was washed and heat set at57° C. for 5 minutes. A circular front half with a 20 cm diameter shapewas cut using a die (see front half 20 of pouch implant in FIG. 2A). Acircular back half 30 with a 12.5 cm diameter was also cut from the meshwith a die (see FIG. 2B). The front half 20 was further cut using aTroTec 400 laser cutter to create a pattern of rectangular holes 26around the perimeter of the circle as shown in FIG. 2A and then the meshwas thermoformed to provide a semi-spherical 3D shape with a 0.5 cm sealarea (shown as the shaded region in FIG. 2A). The P4HB mesh was moldedby mounting the mesh in a three-part metal mold and thermoforming themesh under tension in a hot water bath at 57° C. for 5 minutes. The 3Dmolded mesh was then quenched in a cold-water bath at 9° C. for 10 min,removed from the mold, and dried. The back half 30 circular shape, shownin FIG. 2B, was then attached to the seal region of the semi-sphericaltop half shape using a Brother sewing machine threaded with a USP size6-0 P4HB monofilament fiber using a lock-stitch pattern to preventunraveling of the stitch line. After sewing, the stitched parts weremanually cut using sharp scissors to create a V-shaped slit asillustrated in FIG. 1 . Finally, a draw cord 12 was threaded through thelaser-cut rectangular slots in an alternating pattern as illustrated inFIG. 1 .

Prior to implantation, a breast implant may be inserted into the pouchthrough the V-shaped slit in the pouch, the draw cord pulled tight onthe implant, and the draw cord fastened. The draw cord is tightenedsufficiently to prevent rotation of the implant inside the pouch by morethan 45 degrees, and more preferably by more than 30 degrees. FIG. 3shows a cross-sectional diagram of the breast implant 40 inside the drawcord pouch 10 of FIG. 1 .

Example 2: Pouch with Draw Cord made by Spot Welding

A pouch was formed using the same method disclosed in Example 1, exceptthat spot welding was used to attach the two halves together to form thepouch instead of sewing. An ultrasonic spot welder with a runningfrequency of 20 kHz was used to spot weld the front and back halvestogether in the seal areas 26, 28 shown in FIGS. 2A and 2B.

Example 3: Pouch with Slits to Mate with Breast Implant Tabs

A pouch to limit rotation of a tabbed breast implant was prepared bysolution spinning. FIGS. 4A, 4B illustrate a pouch 110 containing abreast implant with tabs 122 is shown in FIGS. 4A, 4B. The equipment setup used to prepare the pouch is shown in FIG. 5 , and comprised arotating collector 210, solution spinning reservoir, and a spray nozzle220 with a 200 μm diameter orifice connected to a compressed air supply.The collector was formed in the shape of a 250-cm³ round breast implant(12 cm in diameter and 4 cm in height) from aluminum. The reservoir wasfilled with a filtered solution of P4HB comprising an 8% w/v solution ofthe polymer in chloroform. The weight average molecular weight of theP4HB polymer was 340 kDa. The polymer was solution spun onto thecollector using a pump speed of 0.5 mL/min, a compressed air temperatureof 22-29° C., and a pressure of 200 kPa (2 bar). The collector wasrotated at 40 rpm and was placed 60 cm from the spray nozzle duringsolution spinning. The collector was moved during the spinning processso that an even layer of microfibers was deposited on the collector.Solution spinning under these conditions resulted in the formation ofmicrofibers with average diameters ranging from 5 to 30 μm. Collectionof the microfibers on the rotating collector was continued until anonwoven with a thickness of 0.55 mm had been prepared. The nonwoven wasthen removed from the collector by cutting a V-shaped slit in thenonwoven using a sharp blade and removing the pouch from the collectormold. The sharp blade was then used to create four slots in the sides ofthe pouch around its perimeter at 90 degree intervals. The slots werepositioned and sized to receive tabs from a mating breast implant.

Prior to implantation, a breast implant 120 with four mating tabs 122may be inserted into the pouch through the V-shaped slit in the pouch,and the tabs of the implant passed through the slots of the pouch, asillustrated in FIGS. 4 and 6 to prevent rotation of the implant insidethe pouch by more than 45 degrees, and more preferably by more than 30degrees.

Example 4: Pouch with Slit in Base and Small Suture Straps

A pouch 300 to limit rotation of a breast implant with small straps 310on the outer perimeter and a V-shaped slit 320 in the rear or back, asillustrated by FIG. 7 , may be prepared according to the method ofExample 1, but with the following modifications. The circular back halfwith a 12.5 cm diameter is cut with a die, except the mesh is cut toinclude four small suture straps 310 placed every 90 degrees around theperimeter. A slit 320 is then made in the back half, to allow insertionof the implant into the pouch, prior to attaching the back half to thefront half to form the pouch. The slit in the back eliminates the needto make the V-shaped slit 14 shown in FIG. 1 .

Prior to implantation, a breast implant may be inserted into the pouchthrough the V-shaped slit 320 in the back of the pouch, the draw cordpulled tight on the implant, and the draw cord fastened. The draw cordis tightened sufficiently to prevent rotation of the implant inside thepouch by more than 45 degrees, and more preferably by more than 30degrees. The pouch may be anchored to the patient's chest wall bypassing sutures through the small suture straps around the perimeter ofthe pouch.

Modifications and variations of the methods and compositions will beapparent from the foregoing detailed description and are intended tocome within the scope of the appended claims. For instance, the pouchesand enclosures described herein may be shaped to snugly hold and fixateother types of implants in humans, preventing rotation and movement ofthe implant within the pouch, and in embodiments, delivering bioactiveagents from the pouch to prevent infection.

Example 5: Pouch with Slit made by Warp Knitting

A pouch to limit rotation of a round smooth 355 cc breast implant wasmade using a 24-gauge warp knitting machine equipped with a doubleneedle bed using size 6-0 poly-4-hydroxybutyrate (P4HB) monofilamentfiber (weight average molecular weight, Mw=340 kDa) and two guide barswith individual thread guide control. The pick density was set to 10stitches per cm. The fabric was knit as a tubular construct, but whereinareas of the tube were knit together to form a pouch. FIG. 8 is adiagram showing a tubular knit 402 wherein areas of the knit tube werejoined by knitting to form a pouch. The joined areas are denoted byreference numerals 410, 412. In the areas of the knit fabric that arenot connected 402, the fabric is tubular and hollow inside like a hose.The pouch was knit such that the tubular hollow area consisted of closedloop stitches knit separately on the front and back bed, except for theedges 404 where the monofilament fiber was knit simultaneously on thefront and back bed to form the hollow tubular structure. The connectedarea 410, 412 were formed by the combination of open and closed stitchknitting simultaneously on the front and back bed. The knittingdisplacement along the wales in the connected area was 6 loops/cmresulting in a lower semi-circular concave shape 410 as shown in FIG. 8. The knitted pattern was inverted to create an upper semi-circularconvex shape 412 as shown in FIG. 8 .

FIG. 9 is a figure showing a knitted pouch 400. The dimensions of thepouch were 11 cm wide by 11 cm tall and 0.65 mm thickness (includingboth layers of the pouch). An area (440) extends outwards from theconnected area (knitted closure) 430. The extension region was formedduring knitting, and may be used for fixation of the pouch to tissueduring implantation to limit movement of the pouch and breast implant.Additionally, as shown in FIG. 9 , a 6 cm wide slit 450 was cut on oneside of the tubular area of the knit pouch to create an opening forinsertion of a breast implant. The side that the slit is cut ispreferably placed against the chest wall of the patient as discussedabove.

Example 6: Pouch with Slit made by Warp Knitting and Ultrasonic Welding

A pouch to limit rotation of a breast implant may be made using a warpknitting machine to produce a tubular structure as described in Example5, but without forming the connected areas shown in FIG. 8 . Theconnected areas shown in FIG. 8 may be formed instead using anultrasonic welder to form semi-circular heat seals between the layers ofwarp knit. The heat seals so formed create a pouch in the tubularstructure for the implant. A slit may be introduced in the tubular knitfor introduction of the breast implant in the same manner as describedin Example 5.

Example 7: Self-Gripping Resorbable Breast Implant Pouch made fromCircular Cut Warp Knit Mesh

In this example, a pouch for a breast implant was made from a spacermesh that was produced on a 20-gauge double needle bed warp knittingmachine using 120-micron diameter P4HB monofilament fiber with a weightaverage molecular weight of 320 kDa. With reference to FIGS. 11A, 11B, aspacer mesh 540 was made using a honey comb knitting pattern design onboth the front and back needle beds (see FIG. 11A). We observed thatthis allows for good drapability of the pouch around a spherical breastimplant. The knitted spacer mesh 540 had two distinctive pore sizes, 0.1(small) and 9 mm² (large), a thickness (t_(s)) of 7 mm (distance betweenfront and back faces of the mesh shown in FIG. 11B), and an arealdensity of 176 g/m². The spacer mesh was then cut into 10 to 15 cmcircles (FIG. 11A) to accommodate smooth round breast implants withvolumes of 255 cc to 650 cc.

With reference to FIG. 12A, a slit 610 to allow insertion of a breastimplant into the pouch was made on only the first face 612 of the spacermesh 600 using scissors and an offset distance (d_(offset)) from eachedge. In embodiments, the offset distance ranges from 3-8 mm, 4-6 mm,and in some embodiments is about 5 mm.

The pouch 600 after cutting a slit 610 is shown in FIG. 128 .

With reference to FIG. 13A, the interlaced P4HB monofilaments 616connecting the front face 612 and back face 614 of the spacer mesh werecut using a hot knife at 85° C. in the mid-plane (ABC) between the frontand back faces of the meshes, while leaving a 5 mm intact (uncut) region(A_(ur)) along the periphery (as illustrated in FIG. 13A), to create apocket for the breast implant.

FIG. 13B shows an enlarged view of a portion of the spacer fabric afterit has been cut as described above.

Next, and with reference to FIG. 14 , the precursor pouch or pocket ofFIG. 13A was flipped inside-out resulting in a self-gripping pouch 700where cut monofilaments 710, 712, 714 . . . were exposed on the outersurface of the pouch as tissue anchors. The cut monofilaments 710, 712,714, . . . protruded on average 3 mm away from either face of the mesh.The density of anchors was on average 26 anchors/cm² of mesh. Theprotruding anchors may range in length from 1-10 mm, and more preferablyare about 2-4 mm, and in some variations 1-3 mm.

Example 8: Drapable Lightweight Breast Implant Pouch made using OverlookStitch

With reference to FIGS. 15 to 17B, a resorbable pouch for a breastimplant was made from a 14-gauge Marlex mesh knit pattern using100-micron diameter P4HB monofilament with a weight average molecularweight of 310 kDa. The average areal density of the mesh was 48 g/m².The mesh was cut into three parts: two semicircles of 11 cm radius (810and 820) and a full circle of 16 cm diameter (830). The pouch wasassembled by placing the semicircle 810 and semicircle 820 side by sideon top of the full circular cutout (830), and stitched with a 1 cmoverlap between semicircle 810 and semicircle 820 and the full circularcutout (830) along the stitch lines 840 using an overlook stitchconsisting of three separately fed P4HB monofilaments with 2 grams oftension on each. The stitched edge 850 of the pouch is shown in FIG.16A, and a diagram of the stitch pattern 860 is shown in FIG. 16B. Thestitched assembly formed a hemispherical pouch 800 with full circularcutout (830) being the front half of the pouch and (810) and (820)forming the back half of the pouch with a middle opening 850 forinsertion of a breast implant. The front of the pouch 800 with a breastimplant inserted is shown in FIG. 17A, and the back of the pouch 800with a breast implant 870 inserted therein is shown in FIG. 17B.

Example 9: Breast Implant Fixation Device comprising a Pouch withVarying Pore Size and Thickness Assembled with Overlook Stitch

A resorbable pouch for breast implants was made from two types of knitmeshes: mesh (M1) consisting of 14-gauge Marlex knit pattern made with168-micron diameter P4HB monofilament (90% elongation) and an averageareal density of 152 g/m²; and mesh (M2) consisting of 14-gauge Marlexknit pattern made with 120-micron diameter P4HB monofilament (25%elongation) and an areal density of 48 g/m². Both monofilaments had anaverage molecular weight of 310 kDa. Mesh (M1) was not heat set whilemesh (M2) was heat set at 54° C. for 5 min leading respectively topercent elasticities under ball burst of 42% and 18%, thicknesses of0.75 mm and 0.38 mm, and average major pore diameter sizes of 0.35 and0.42 mm.

A drapable breast implant fixation device was prepared by forming apouch from the two meshes, M1 and M2. The pouch was constructed fromthree parts: two semicircular pieces of mesh M2 of 11 cm radius (shownas 810 and 820 in FIG. 15 ) and a round piece of mesh M1 of 16 cmdiameter (shown as 830 in FIG. 15 ). The semicircular pieces were placedside by side on the round cutout with a 1 cm overlap as shown in FIG. 15, and stitched together using an overlook stitch (as shown in FIG. 16B)consisting of three separately fed 100-micron P4HB monofilaments with 2grams of tension on each. The stitched assembly formed a hemisphericalpouch with 830 being the front half of the pouch with a thickness of0.75 mm, pore size of 0.35 mm, and elasticity of 42%, and (810) and(820) forming the back half of the pouch with a thickness of 0.38 mm,pore size of 0.42 mm, elasticity of 18%, and a middle opening on thebottom half for insertion of a breast implant.

Example 10: Breast Implant Fixation Device comprising a Pouch withVarying Pore Size and Thickness Assembled with Ultrasonic Welding

In this example, a breast implant fixation device 880 was prepared asdescribed in Example 9, except that the pouch was formed byultrasonically welding the meshes 810 and 820 to mesh 830 using a 1 mmwide rotary horn set at a 20 kHz frequency, 45 microns amplitude, and 48psi pressure.

Example 11: Breast Implant Fixation Device comprising a Pouch withVarying Pore Size and Thickness Assembled with Ultrasonic Welding

In this example, a resorbable pouch for fixation of breast implants wasprepared as described in Example 10, except that front face 830′ wasprepared by ultrasonically welding together, at discrete points 870evenly spaced in a 2 cm diamond pattern as shown in FIG. 18 , threepre-cut round pieces of mesh 832, 834, 836. Welding of the three roundpieces of mesh resulted in the front half of the pouch having athickness of 2.25 mm.

We claim:
 1. A breast implant fixation device to limit migration of abreast implant in a patient comprising: a pouch comprising a shape andsize to at least partially cover the breast implant; a plurality ofpores for tissue to grow therein and secure the device to the patient;wherein the pouch comprises a back area for placement on the chest wallof the patient, a front area opposite the back area, the front areacomprising a front bottom for placement in the lower pole of the breast,a front top for placement in the upper pole of the breast, and a frontintermediate-region for placement under the skin of the patient; andwherein at least a portion of the front area of the pouch is thickerthan the back area of the pouch.
 2. The device of claim 1, wherein thethickness of the front area of the pouch is sufficient to prevent thebreast implant from being palpable, or to hide any ripples orindentations in the skin of the patient, when a breast implant is placedin the pouch, and the pouch is implanted in the breast of the patient.3. The device of claim 1, wherein the front area of the pouch has anelasticity range of 30-65%, wherein the elasticity is measured as thepercent increase in an area when an area is subject to deformation inASTM burst method D6797-02 using a round ball.
 4. The device of claim 1,wherein the back area of the pouch has an elasticity range of 8-20%,wherein the elasticity is measured as the percent increase in an areawhen an area is subject to deformation in ASTM burst method D6797-02using a round ball.
 5. The device of claim 1, wherein the pouch has atleast one of the following thicknesses: a thickness of the front area ofthe pouch between 0.75-3 mm, and a thickness of the back area of thepouch between 0.2-0.4 mm.
 6. A breast implant fixation device to limitmigration of a breast implant in a patient comprising: a pouchcomprising a shape and size to at least partially cover the breastimplant; a plurality of pores for tissue to grow therein, securing thedevice to the patient anatomy; wherein the pouch comprises a back areafor placement on the chest wall of the patient, a front area oppositethe back area, the front area comprising a front bottom for placement inthe lower pole of the breast, a front top for placement in the upperpole of the breast, and a front intermediate-region for placement underthe skin of the patient; and wherein the back area has a differentelasticity than the front area.
 7. The device of claim 6, wherein thefront area of the pouch has an elasticity of 30-65%, wherein theelasticity is measured as the percent increase of the area when the areais subject to deformation in ASTM burst method D6797-02 using a roundball.
 8. The device of claim 7, wherein the back area of the pouch hasan elasticity 8-20%, wherein the elasticity is measured as the percentincrease of the area when the area is subject to deformation in ASTMburst method D6797-02 using a round ball.
 9. The device of claim 6,wherein the pouch is shaped to enclose a breast implant.
 10. The deviceof claim 6, wherein the pouch comprises at least one seam connecting theback area of the pouch with the front intermediate-region, front top orfront bottom of the pouch.
 11. The device of claim 6, wherein the pouchhas one or more of the following pore sizes: an average pore diameter inthe back area of the pouch between 0.5 mm and 3 mm, an average porediameter in the front bottom of the pouch between 0.5 mm and 1 mm, andan average pore diameter in the front top of the pouch between 0.1 mmand 1 mm.
 12. The device of claim 6, wherein the pouch comprises one ormore of the following: a textile, woven textile, non-woven textile,monofilament mesh, or multifilament mesh.
 13. The device of claim 12,wherein the textile, woven textile, non-woven textile, monofilamentmesh, or multifilament mesh has at least one of the followingproperties: (i) burst strength of 0.1 to 30 kgf/cm²; (ii) suture pulloutstrength of 1 to 7 kgf; and (iii) areal density of 40 to 190 g/m². 14.The device of claim 6, wherein the back area of the pouch comprises aslit or opening to allow insertion of the breast implant into the pouch.15. The device of claim 6, wherein the pouch further comprises one ormore of the following: a draw cord, a securing element to maintain thebreast implant in fixed alignment with the pouch, and a slot orreceptacle to engage a protuberance from a breast implant.
 16. Thedevice of claim 6, wherein the pouch comprises a resorbable polymer. 17.The device of claim 6, wherein the resorbable polymer ispoly-4-hydroxybutyrate or copolymer thereof, or poly(butylene succinate)or copolymer thereof.
 18. The device of claim 6, wherein the pouchfurther comprises one or more of the following: an additive, bioactiveagent, antibiotic, antimicrobial, autologous fat, fat lipoaspirate,injectable fat, adipose cells, fibroblast cells, stem cells, collagen,and hyaluronic acid.
 19. The device of claim 6, wherein an endotoxincontent of the device is less than 20 endotoxin units, and the device issterile.
 20. The device of claim 6, wherein the thickness of the frontarea of the pouch decreases from the upper pole to the lower pole. 21.The device of claim 6, wherein the elasticity of the front area of thepouch increases from the upper pole to the lower pole.
 22. A method ofmaking a pouch to limit movement of a breast implant in a patientcomprising: forming a pouch in the shape of a breast implant and in asize to at least partially cover the breast implant, and carrying outthe forming step such that a slit or opening is provided in a back areaof the pouch to allow insertion of the breast implant.
 23. The method ofclaim 22, wherein the step of forming the pouch is performed by forminga front area comprising a front bottom for placement in the lower poleof the breast, a front top for placement in the upper pole of thebreast, and a front intermediate-region for placement under the skin ofthe patient; and wherein the front area of the pouch is thicker than theback area of the pouch.
 24. The method of claim 22, wherein the step offorming the pouch is performed by forming a front area comprising afront bottom for placement in the lower pole of the breast, a front topfor placement in the upper pole of the breast, and a frontintermediate-region for placement under the skin of the patient; andwherein the pouch has one or more of the following elasticities: anelasticity of the front area of the pouch of 15-75%, and an elasticityof the back area of the pouch of 5-25%, wherein the elasticity ismeasured as the percent increase of the area when the area is subject todeformation in ASTM burst method D6797-02 using a round ball.
 25. Themethod of claim 23, wherein the step of forming the pouch is performedby forming the back area with a different elasticity than the frontarea.
 26. A method of implanting the device of claim 1, comprising:selecting the pouch; placing a breast implant inside the pouch; locatingthe pouch containing the breast implant in the breast of a patient, andsecuring the pouch to the patient, and optionally, wherein the securingis performed by securing the pouch to the chest wall of the patient.